27,175 results on '"Clinical Genetics"'
Search Results
2. Pathogenic variants in the Longitudinal Early‐onset Alzheimer's Disease Study cohort
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Nudelman, Kelly NH, Jackson, Trever, Rumbaugh, Malia, Eloyan, Ani, Abreu, Marco, Dage, Jeffrey L, Snoddy, Casey, Faber, Kelley M, Foroud, Tatiana, Hammers, Dustin B, Committee, DIAN DIAN‐TU Clinical Genetics, Taurone, Alexander, Thangarajah, Maryanne, Aisen, Paul, Beckett, Laurel, Kramer, Joel, Koeppe, Robert, Kukull, Walter A, Murray, Melissa E, Toga, Arthur W, Vemuri, Prashanthi, Atri, Alireza, Day, Gregory S, Duara, Ranjan, Graff‐Radford, Neill R, Honig, Lawrence S, Jones, David T, Masdeu, Joseph C, Mendez, Mario, Musiek, Erik, Onyike, Chiadi U, Riddle, Meghan, Rogalski, Emily, Salloway, Stephen, Sha, Sharon J, Turner, R Scott, Wingo, Thomas S, Wolk, David A, Carrillo, Maria C, Dickerson, Bradford C, Rabinovici, Gil D, Apostolova, Liana G, and Consortium, the LEADS
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Biomedical and Clinical Sciences ,Biological Psychology ,Clinical Sciences ,Neurosciences ,Psychology ,Dementia ,Alzheimer's Disease ,Clinical Research ,Acquired Cognitive Impairment ,Neurodegenerative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Genetics ,Aging ,Brain Disorders ,2.1 Biological and endogenous factors ,Neurological ,Humans ,Alzheimer Disease ,Amyloid beta-Protein Precursor ,C9orf72 Protein ,Genetic Testing ,Longitudinal Studies ,Mutation ,Presenilin-1 ,Presenilin-2 ,Alzheimer's disease ,APP ,C9ORF7 ,dementia ,early onset ,genetics ,GRN ,MAPT ,PSEN1 ,PSEN2 ,sequencing ,DIAN/DIAN-TU Clinical/Genetics Committee ,LEADS Consortium ,Geriatrics ,Clinical sciences ,Biological psychology - Abstract
IntroductionOne goal of the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is to investigate the genetic etiology of early onset (40-64 years) cognitive impairment. Toward this goal, LEADS participants are screened for known pathogenic variants.MethodsLEADS amyloid-positive early-onset Alzheimer's disease (EOAD) or negative early-onset non-AD (EOnonAD) cases were whole exome sequenced (N = 299). Pathogenic variant frequency in APP, PSEN1, PSEN2, GRN, MAPT, and C9ORF72 was assessed for EOAD and EOnonAD. Gene burden testing was performed in cases compared to similar-age cognitively normal controls in the Parkinson's Progression Markers Initiative (PPMI) study.ResultsPreviously reported pathogenic variants in the six genes were identified in 1.35% of EOAD (3/223) and 6.58% of EOnonAD (5/76). No genes showed enrichment for carriers of rare functional variants in LEADS cases.DiscussionResults suggest that LEADS is enriched for novel genetic causative variants, as previously reported variants are not observed in most cases.HighlightsSequencing identified eight cognitively impaired pathogenic variant carriers. Pathogenic variants were identified in PSEN1, GRN, MAPT, and C9ORF72. Rare variants were not enriched in APP, PSEN1/2, GRN, and MAPT. The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is a key resource for early-onset Alzheimer's genetic research.
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- 2023
3. Intravenous vs. Oral Hydration to Reduce the Risk of Post-Contrast Acute Kidney Injury After Intravenous Contrast-Enhanced Computed Tomography in Patients With Severe Chronic Kidney Disease (ENRICH)
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Department of Nephrology, Odense University Hospital, Department of Clinical Genetics, Odense University Hospital, The A.P. Moller Foundation, The Research Counsil of Odense University Hospital, Copenhagen University's Research Foundation for Medical Students, Helen and Ejnar Bjørnow's Foundation, Novo Nordisk A/S, Sophus Jacobsen and Astrid Jacobsen's Foundation, Open Patient data Explorative Network (OPEN), and Emil Johannes Ravn, Medical student and clinical research assistant
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- 2023
4. The Importance of Copy Number Variant Analysis in Patients with Monogenic Kidney Disease
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Cancer, Genetica Oper.Mang. Clinical Genetics, Genetica Medische Informatica, Child Health, Genetica Sectie Genoomdiagnostiek, Genetica Klinische Genetica, Claus, Laura R., Ernst, Robert F., Elferink, Martin G., van Deutekom, Hanneke W.M., van der Zwaag, Bert, van Eerde, Albertien M., Cancer, Genetica Oper.Mang. Clinical Genetics, Genetica Medische Informatica, Child Health, Genetica Sectie Genoomdiagnostiek, Genetica Klinische Genetica, Claus, Laura R., Ernst, Robert F., Elferink, Martin G., van Deutekom, Hanneke W.M., van der Zwaag, Bert, and van Eerde, Albertien M.
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- 2024
5. Comparison of clinical selection-based genetic testing with phenotype-agnostic extensive germline sequencing to diagnose genetic predisposition in children with cancer: a prospective diagnostic study
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Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Pathologie Pathologen staf, PMC Medisch specialisten, Onderzoek Beeld, Genetica Klinische Genetica, Child Health, Bakhuizen, Jette J., van Dijk, Freerk, Koudijs, Marco J., Bladergroen, Reno S., Bon, Sebastian B.B., Hopman, Saskia M.J., Kester, Lennart A., Kranendonk, Mariëtte E.G., Loeffen, Jan L.C., Smetsers, Stephanie E., Sonneveld, Edwin, Tachdjian, Melissa, de Vos-Kerkhof, Evelien, Goudie, Catherine, Merks, Johannes H.M., Kuiper, Roland P., Jongmans, Marjolijn C.J., Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Pathologie Pathologen staf, PMC Medisch specialisten, Onderzoek Beeld, Genetica Klinische Genetica, Child Health, Bakhuizen, Jette J., van Dijk, Freerk, Koudijs, Marco J., Bladergroen, Reno S., Bon, Sebastian B.B., Hopman, Saskia M.J., Kester, Lennart A., Kranendonk, Mariëtte E.G., Loeffen, Jan L.C., Smetsers, Stephanie E., Sonneveld, Edwin, Tachdjian, Melissa, de Vos-Kerkhof, Evelien, Goudie, Catherine, Merks, Johannes H.M., Kuiper, Roland P., and Jongmans, Marjolijn C.J.
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- 2024
6. Identification of a pathogenic deep intronic variant in ATRX ends a diagnostic odyssey
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Genetica, Genetica Klinische Genetica, Circulatory Health, Genetica Sectie Genoomdiagnostiek, Genetica Oper.Mang. Clinical Genetics, Child Health, Algemeen management, Cluster D, Integrale & Alg. Kindergen Patientenzorg, van der Smagt, Jasper J., Lampri, Angeliki P., de Lange, Iris, Alders, Mariëlle, Houben, Michiel L., Koudijs, Marco J., van Jaarsveld, Richard H., Genetica, Genetica Klinische Genetica, Circulatory Health, Genetica Sectie Genoomdiagnostiek, Genetica Oper.Mang. Clinical Genetics, Child Health, Algemeen management, Cluster D, Integrale & Alg. Kindergen Patientenzorg, van der Smagt, Jasper J., Lampri, Angeliki P., de Lange, Iris, Alders, Mariëlle, Houben, Michiel L., Koudijs, Marco J., and van Jaarsveld, Richard H.
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- 2024
7. Medulloblastomas with ELP1 pathogenic variants: A weakly penetrant syndrome with a restricted spectrum in a limited age window
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Genetica, Genetica Oper.Mang. Clinical Genetics, Guerrini-Rousseau, Léa, Masliah-Planchon, Julien, Filser, Mathilde, Tauziède-Espariat, Arnault, Entz-Werle, Natacha, Maugard, Christine M., Hopman, Saskia M.J., Torrejon, Jacob, Gauthier-Villars, Marion, Simaga, Fatoumata, Blauwblomme, Thomas, Beccaria, Kevin, Rouleau, Etienne, Dimaria, Marina, Grill, Jacques, Abbou, Samuel, Claret, Béatrice, Brugières, Laurence, Doz, François, Bouchoucha, Yassine, Faure-Conter, Cécile, Bonadona, Valerie, Mansuy, Ludovic, De Carli, Emilie, Ingster, Olivier, Legrand, Clémentine, Pagnier, Anne, Berthet, Pascaline, Bodet, Damien, Julia, Sophie, Bertozzi, Anne Isabelle, Wilems, Marjolaine, Maurage, Claude Alain, Delattre, Olivier, Ayrault, Olivier, Dufour, Christelle, Bourdeaut, Franck, Genetica, Genetica Oper.Mang. Clinical Genetics, Guerrini-Rousseau, Léa, Masliah-Planchon, Julien, Filser, Mathilde, Tauziède-Espariat, Arnault, Entz-Werle, Natacha, Maugard, Christine M., Hopman, Saskia M.J., Torrejon, Jacob, Gauthier-Villars, Marion, Simaga, Fatoumata, Blauwblomme, Thomas, Beccaria, Kevin, Rouleau, Etienne, Dimaria, Marina, Grill, Jacques, Abbou, Samuel, Claret, Béatrice, Brugières, Laurence, Doz, François, Bouchoucha, Yassine, Faure-Conter, Cécile, Bonadona, Valerie, Mansuy, Ludovic, De Carli, Emilie, Ingster, Olivier, Legrand, Clémentine, Pagnier, Anne, Berthet, Pascaline, Bodet, Damien, Julia, Sophie, Bertozzi, Anne Isabelle, Wilems, Marjolaine, Maurage, Claude Alain, Delattre, Olivier, Ayrault, Olivier, Dufour, Christelle, and Bourdeaut, Franck
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- 2024
8. Molecular analysis of cancer genomes in children with Lynch syndrome: Exploring causal associations
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Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Pathologie patiënten zorg, Pathologie Groep Van Diest, Genetica Klinische Genetica, Child Health, Weijers, Dilys D., Hirsch, Steffen, Bakhuizen, Jette J., van Engelen, Nienke, Kester, Lennart A., Kranendonk, Mariëtte E.G., Hiemcke-Jiwa, Laura S., de Vos-Kerkhof, Evelien, Loeffen, Jan L.C., Autry, Robert J., Pajtler, Kristian W., Jäger, Natalie, Jongmans, Marjolijn C.J., Kuiper, Roland P., Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Pathologie patiënten zorg, Pathologie Groep Van Diest, Genetica Klinische Genetica, Child Health, Weijers, Dilys D., Hirsch, Steffen, Bakhuizen, Jette J., van Engelen, Nienke, Kester, Lennart A., Kranendonk, Mariëtte E.G., Hiemcke-Jiwa, Laura S., de Vos-Kerkhof, Evelien, Loeffen, Jan L.C., Autry, Robert J., Pajtler, Kristian W., Jäger, Natalie, Jongmans, Marjolijn C.J., and Kuiper, Roland P.
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- 2024
9. GeNepher data- and biobank for patients with (suspected) genetic kidney disease: Rationale, design and status update
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Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Groep Van Tintelen, Genetica Sectie Genoomdiagnostiek, Child Health, Epi Methoden Team 2, Regenerative Medicine and Stem Cells, MS Nefrologie, Nefrologie, Genetica Klinische Genetica, Claus, Laura R., Lekkerkerker, Iris, van der Zwaag, Bert, Nguyen, Tri Q., Knoers, Nine V.A.M., de Borst, Martin H., Rookmaker, Maarten B., Lilien, Marc R., van Eerde, Albertien M., Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Groep Van Tintelen, Genetica Sectie Genoomdiagnostiek, Child Health, Epi Methoden Team 2, Regenerative Medicine and Stem Cells, MS Nefrologie, Nefrologie, Genetica Klinische Genetica, Claus, Laura R., Lekkerkerker, Iris, van der Zwaag, Bert, Nguyen, Tri Q., Knoers, Nine V.A.M., de Borst, Martin H., Rookmaker, Maarten B., Lilien, Marc R., and van Eerde, Albertien M.
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- 2024
10. No Pathogenic DICER1 Gene Variants in a Cohort Study of 28 Children With Congenital Pulmonary Airway Malformation
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Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Klinische Genetica, Child Health, Onderzoek Beeld, Bakhuizen, Jette J., Postema, Floor A.M., van Rijn, Rick R., van Schuppen, Joost, Duijkers, Floor A.M., van Noesel, Carel J.M., Hennekam, Raoul C., Jongmans, Marjolijn C.J., Savci-Heijink, C. Dilara, Smetsers, Stephanie E., Terheggen-Lagro, Suzanne W.J., Hopman, Saskia M.J., Oomen, Matthijs W.N., Merks, Johannes H.M., Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Klinische Genetica, Child Health, Onderzoek Beeld, Bakhuizen, Jette J., Postema, Floor A.M., van Rijn, Rick R., van Schuppen, Joost, Duijkers, Floor A.M., van Noesel, Carel J.M., Hennekam, Raoul C., Jongmans, Marjolijn C.J., Savci-Heijink, C. Dilara, Smetsers, Stephanie E., Terheggen-Lagro, Suzanne W.J., Hopman, Saskia M.J., Oomen, Matthijs W.N., and Merks, Johannes H.M.
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- 2024
11. A new variant in the ZCCHC8 gene: diverse clinical phenotypes and expression in the lung
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Researchafd. Longtransplantatie, Genetica Oper.Mang. Clinical Genetics, Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Longziekten, Infection & Immunity, Groen, Karlijn, van der Vis, Joanne J, van Batenburg, Aernoud A, Kazemier, Karin M, de Bruijn, Marjolein J W, Stadhouders, Ralph, Arp, Pascal, Verkerk, Annemieke J M H, Schoemaker, Angela E, de Bie, Charlotte I, Massink, Maarten P G, van Beek, Frouke T, Grutters, Jan C, Vergouw, Leonie J M, van Moorsel, Coline H M, Researchafd. Longtransplantatie, Genetica Oper.Mang. Clinical Genetics, Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Longziekten, Infection & Immunity, Groen, Karlijn, van der Vis, Joanne J, van Batenburg, Aernoud A, Kazemier, Karin M, de Bruijn, Marjolein J W, Stadhouders, Ralph, Arp, Pascal, Verkerk, Annemieke J M H, Schoemaker, Angela E, de Bie, Charlotte I, Massink, Maarten P G, van Beek, Frouke T, Grutters, Jan C, Vergouw, Leonie J M, and van Moorsel, Coline H M
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- 2024
12. Genotype–phenotype associations in 1018 individuals with SCN1A-related epilepsies
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Genetica, Genetica Klinische Genetica, Brain, Genetica Oper.Mang. Clinical Genetics, Child Health, Gallagher, Declan, Pérez-Palma, Eduardo, Bruenger, Tobias, Ghanty, Ismael, Brilstra, Eva, Ceulemans, Berten, Chemaly, Nicole, de Lange, Iris, Depienne, Christel, Guerrini, Renzo, Mei, Davide, Møller, Rikke S., Nabbout, Rima, Regan, Brigid M., Schneider, Amy L., Scheffer, Ingrid E., Schoonjans, An Sofie, Symonds, Joseph D., Weckhuysen, Sarah, Zuberi, Sameer M., Lal, Dennis, Brunklaus, Andreas, Genetica, Genetica Klinische Genetica, Brain, Genetica Oper.Mang. Clinical Genetics, Child Health, Gallagher, Declan, Pérez-Palma, Eduardo, Bruenger, Tobias, Ghanty, Ismael, Brilstra, Eva, Ceulemans, Berten, Chemaly, Nicole, de Lange, Iris, Depienne, Christel, Guerrini, Renzo, Mei, Davide, Møller, Rikke S., Nabbout, Rima, Regan, Brigid M., Schneider, Amy L., Scheffer, Ingrid E., Schoonjans, An Sofie, Symonds, Joseph D., Weckhuysen, Sarah, Zuberi, Sameer M., Lal, Dennis, and Brunklaus, Andreas
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- 2024
13. Genetic testing for childhood cancer predisposition syndromes: Controversies and recommendations from the SIOPE Host Genome Working Group meeting 2022
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Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Klinische Genetica, Child Health, SIOPE Host Genome Working Group, Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Klinische Genetica, Child Health, and SIOPE Host Genome Working Group
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- 2024
14. Medullary Sponge Kidney and its Relationship with Primary Distal Renal Tubular Acidosis: Case Reports and a Comprehensive Genetics First Approach
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Nefrologie patientenzorg, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Sectie Genoomdiagnostiek, Child Health, Unit Opleiding Aios, Nefrologie, Genetica Klinische Genetica, Genomics England Research Consortium, Nefrologie patientenzorg, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Sectie Genoomdiagnostiek, Child Health, Unit Opleiding Aios, Nefrologie, Genetica Klinische Genetica, and Genomics England Research Consortium
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- 2024
15. Experiences of pediatric cancer patients (age 12–18 years) with extensive germline sequencing for cancer predisposition: a qualitative study
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Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Klinische Genetica, Child Health, Speerpunt, Zorg en O&O, Bon, Sebastian B.B., Wouters, Roel H.P., Bakhuizen, Jette J., Jongmans, Marjolijn C.J., van den Heuvel-Eibrink, Marry M., Grootenhuis, Martha A., Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Klinische Genetica, Child Health, Speerpunt, Zorg en O&O, Bon, Sebastian B.B., Wouters, Roel H.P., Bakhuizen, Jette J., Jongmans, Marjolijn C.J., van den Heuvel-Eibrink, Marry M., and Grootenhuis, Martha A.
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- 2024
16. Tumor Syndromes That Include Bone Tumors: An Update
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Gnoli, Maria, Ponti, Francesca, and Sangiorgi, Luca
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- 2017
- Full Text
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17. Development and Developmental Disorders of the Brain Stem
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Genetica Oper.Mang. Clinical Genetics, Donkelaar, Hans J. ten, Lammens, Martin, Hori, Akira, ten Donkelaar, Hans J., Fritzsch, Bernd, Cruysberg, Johannes R.M., Pennings, Ronald J.E., Smits, Jeroen J., Genetica Oper.Mang. Clinical Genetics, Donkelaar, Hans J. ten, Lammens, Martin, Hori, Akira, ten Donkelaar, Hans J., Fritzsch, Bernd, Cruysberg, Johannes R.M., Pennings, Ronald J.E., and Smits, Jeroen J.
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- 2023
18. The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder
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Genetica Sectie Genoomdiagnostiek, Genetica Oper.Mang. Clinical Genetics, Child Health, Genetica Klinische Genetica, Genomics England Research Consortium, Genetica Sectie Genoomdiagnostiek, Genetica Oper.Mang. Clinical Genetics, Child Health, Genetica Klinische Genetica, and Genomics England Research Consortium
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- 2023
19. Rhabdomyolysis, encephalopathy, epilepsy and cardiac arrhythmia
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Medische Staf Intensive Care, UMC Krant, Genetica Oper.Mang. Clinical Genetics, Genetica Sectie Genoomdiagnostiek, Projectafdeling functional imaging, Neurologen, Metabole ziekten patientenzorg, Toeback, Jonas, De Pagter, Mirjam, Exalto, Lieza, Koop, K, Van Der Heijden, Joris, Medische Staf Intensive Care, UMC Krant, Genetica Oper.Mang. Clinical Genetics, Genetica Sectie Genoomdiagnostiek, Projectafdeling functional imaging, Neurologen, Metabole ziekten patientenzorg, Toeback, Jonas, De Pagter, Mirjam, Exalto, Lieza, Koop, K, and Van Der Heijden, Joris
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- 2023
20. KidneyNetwork: using kidney-derived gene expression data to predict and prioritize novel genes involved in kidney disease
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Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Sectie Genoomdiagnostiek, Child Health, MS Nefrologie, Circulatory Health, Genetica Klinische Genetica, Genomics England Research Consortium, Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Sectie Genoomdiagnostiek, Child Health, MS Nefrologie, Circulatory Health, Genetica Klinische Genetica, and Genomics England Research Consortium
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- 2023
21. Surgical Oncologists and Nurses in Breast Cancer Care are Ready to Provide Pre-Test Genetic Counseling
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Cancer, Genetica Sectie Oncogenetica, Genetica Klinische Genetica, MS CGO, Genetica, Genetica Oper.Mang. Clinical Genetics, Staf strategisch beleid, Genetica Sectie Genoomdiagnostiek, Bokkers, K., Bleiker, E. M.A., Aalfs, C. M., van Dalen, T., Velthuizen, M. E., Duijveman, P., Sijmons, R. H., Koole, W., Schoenmaeckers, E. J.P., Ausems, M. G.E.M., Cancer, Genetica Sectie Oncogenetica, Genetica Klinische Genetica, MS CGO, Genetica, Genetica Oper.Mang. Clinical Genetics, Staf strategisch beleid, Genetica Sectie Genoomdiagnostiek, Bokkers, K., Bleiker, E. M.A., Aalfs, C. M., van Dalen, T., Velthuizen, M. E., Duijveman, P., Sijmons, R. H., Koole, W., Schoenmaeckers, E. J.P., and Ausems, M. G.E.M.
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- 2023
22. Assessment of Cancer Predisposition Syndromes in a National Cohort of Children With a Neoplasm
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Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Child Health, Speerpunt, Zorg en O&O, Genetica Klinische Genetica, Pathologie Moleculair, Genetica Sectie Genoomdiagnostiek, PMC Medisch specialisten, Onderzoek Beeld, Bakhuizen, Jette J., Hopman, Saskia M.J., Bosscha, Machteld I., Dommering, Charlotte J., van den Heuvel-Eibrink, Marry M., Hol, Janna A., Kester, Lennart A., Koudijs, Marco J., Langenberg, Karin P.S., Loeffen, Jan L.C., van der Lugt, Jasper, Moll, Annette C., van Noesel, Max M., Smetsers, Stephanie E., de Vos-Kerkhof, Evelien, Merks, Johannes H.M., Kuiper, Roland P., Jongmans, Marjolijn C.J., Genetica, Genetica Oper.Mang. Clinical Genetics, Cancer, Child Health, Speerpunt, Zorg en O&O, Genetica Klinische Genetica, Pathologie Moleculair, Genetica Sectie Genoomdiagnostiek, PMC Medisch specialisten, Onderzoek Beeld, Bakhuizen, Jette J., Hopman, Saskia M.J., Bosscha, Machteld I., Dommering, Charlotte J., van den Heuvel-Eibrink, Marry M., Hol, Janna A., Kester, Lennart A., Koudijs, Marco J., Langenberg, Karin P.S., Loeffen, Jan L.C., van der Lugt, Jasper, Moll, Annette C., van Noesel, Max M., Smetsers, Stephanie E., de Vos-Kerkhof, Evelien, Merks, Johannes H.M., Kuiper, Roland P., and Jongmans, Marjolijn C.J.
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- 2023
23. [Clinical practice guidelines for Fragile X syndrome]
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Clinical Genetics Group Of Medical Geneticist Branch Of Chinese Medical Doctor Association, Clinical Genetics Group Of Medical Genetics Branch Of Chinese Medical Association, Genetic Disease Prevention And Control Group Of Professional Committee For Birth Defect Prevention And Control Of Chinese Preventive Medicine Association, Ranhui, Duan, Guangxu, Li, Hui, Xi, Ying, Peng, and Lingqian, Wu
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Fragile X Mental Retardation Protein ,Autism Spectrum Disorder ,Fragile X Syndrome ,Intellectual Disability ,Humans ,Child - Abstract
Fragile X syndrome (FXS) is the most common monogenic form of inherited intellectual disability and autism spectrum disorder (ASD). More than 99% of individuals with FXS are caused by the unstable expansion of CGG repeats located within the 5'-untranslated region of the FMR1 gene. The clinical features of FXS include various degrees of cognitive deficit, physical, behavioral and psychiatric problems. Early treatment and prevention from having further affected children can be guided by molecular genetic testing of the FMR1 gene. The following guideline has combined the relevant research, guidelines and consensus worldwide, and summarized the genetic knowledge and clinical treatment for FXS in order to achieve a standardized diagnosis, treatment and prevention for patients and families affected by this disease.
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- 2022
24. Review of genetic testing in kidney disease patients: Diagnostic yield of single nucleotide variants and copy number variations evaluated across and within kidney phenotype groups
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Genetica Oper.Mang. Clinical Genetics, Cancer, MS Verloskunde, Genetica, Genetica Klinische Genetica, Child Health, Claus, Laura R, Snoek, Rozemarijn, Knoers, Nine V A M, van Eerde, Albertien M, Genetica Oper.Mang. Clinical Genetics, Cancer, MS Verloskunde, Genetica, Genetica Klinische Genetica, Child Health, Claus, Laura R, Snoek, Rozemarijn, Knoers, Nine V A M, and van Eerde, Albertien M
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- 2022
25. MO047: Biallelic pathogenic variants in ROBO1 associate with syndromic CAKUT
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Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Klinische Genetica, Child Health, Muench, Johannes, Engesser, Marie, Schoenauer, Ria, Hamm, J. Austin, Akay, Gulsen, Tueysuez, Beyhan, Shirakawa, Toshihiko, Dateki, Sumito, Claus, Laura, van Eerde, Albertien M., Wagner, Timo, Bergmann, Carsten, Buchan, Jillian, Wegner, Tara, Posey, Jennifer, Lupski, James R., Petit, Florence, Mccarthy, Andrew A., Pazour, Gregory J., Lo, Cecilia W., Popp, Bernt, Halbritter, Jan, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Klinische Genetica, Child Health, Muench, Johannes, Engesser, Marie, Schoenauer, Ria, Hamm, J. Austin, Akay, Gulsen, Tueysuez, Beyhan, Shirakawa, Toshihiko, Dateki, Sumito, Claus, Laura, van Eerde, Albertien M., Wagner, Timo, Bergmann, Carsten, Buchan, Jillian, Wegner, Tara, Posey, Jennifer, Lupski, James R., Petit, Florence, Mccarthy, Andrew A., Pazour, Gregory J., Lo, Cecilia W., Popp, Bernt, and Halbritter, Jan
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- 2022
26. Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'
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Genetica Oper.Mang. Clinical Genetics, Cancer, PMC Medisch specialisten, Arts-assistenten Kinderen, Groep Holstege, Pathologie Pathologen staf, Pathologie Groep Van Diest, Brain, Hematologie ICAT, Infection & Immunity, CDL Cluster Onderzoek en Onderwijs, Pathologie Moleculair, Genetica Sectie Genoomdiagnostiek, Onderzoek Beeld, Child Health, Neurochirurgen, Zorg en O&O, Genetica Klinische Genetica, Genetica, Zorgeenheid Kinderchirurgie Medisch, Speerpunt, CMM, Langenberg, Karin P S, Meister, Michael T, Bakhuizen, Jette J, Boer, Judith M, van Eijkelenburg, Natasha K A, Hulleman, Esther, Ilan, Uri, Looze, Eleonora J, Dierselhuis, Miranda P, van der Lugt, Jasper, Breunis, Willemijn, Schild, Linda G, Ober, Kimberley, van Hooff, Sander R, Scheijde-Vermeulen, Marijn A, Hiemcke-Jiwa, Laura S, Flucke, Uta E, Kranendonk, Mariette E G, Wesseling, Pieter, Sonneveld, Edwin, Punt, Simone, Boltjes, Arjan, van Dijk, Freerk, Verwiel, Eugene T P, Volckmann, Richard, Hehir-Kwa, Jayne Y, Kester, Lennart A, Koudijs, Marco M J, Waanders, Esme, Holstege, Frank C P, Vormoor, H Josef, Hoving, Eelco W, van Noesel, Max M, Pieters, Rob, Kool, Marcel, Stumpf, Miriam, Blattner-Johnson, Mirjam, Balasubramanian, Gnana P, Van Tilburg, Cornelis M, Jones, Barbara C, Jones, David T W, Witt, Olaf, Pfister, Stefan M, Jongmans, Marjolijn C J, Kuiper, Roland P, de Krijger, Ronald R, Wijnen, Marc H W, den Boer, Monique L, Zwaan, C Michel, Kemmeren, Patrick, Koster, Jan, Tops, Bastiaan B J, Goemans, Bianca F, Molenaar, Jan J, Genetica Oper.Mang. Clinical Genetics, Cancer, PMC Medisch specialisten, Arts-assistenten Kinderen, Groep Holstege, Pathologie Pathologen staf, Pathologie Groep Van Diest, Brain, Hematologie ICAT, Infection & Immunity, CDL Cluster Onderzoek en Onderwijs, Pathologie Moleculair, Genetica Sectie Genoomdiagnostiek, Onderzoek Beeld, Child Health, Neurochirurgen, Zorg en O&O, Genetica Klinische Genetica, Genetica, Zorgeenheid Kinderchirurgie Medisch, Speerpunt, CMM, Langenberg, Karin P S, Meister, Michael T, Bakhuizen, Jette J, Boer, Judith M, van Eijkelenburg, Natasha K A, Hulleman, Esther, Ilan, Uri, Looze, Eleonora J, Dierselhuis, Miranda P, van der Lugt, Jasper, Breunis, Willemijn, Schild, Linda G, Ober, Kimberley, van Hooff, Sander R, Scheijde-Vermeulen, Marijn A, Hiemcke-Jiwa, Laura S, Flucke, Uta E, Kranendonk, Mariette E G, Wesseling, Pieter, Sonneveld, Edwin, Punt, Simone, Boltjes, Arjan, van Dijk, Freerk, Verwiel, Eugene T P, Volckmann, Richard, Hehir-Kwa, Jayne Y, Kester, Lennart A, Koudijs, Marco M J, Waanders, Esme, Holstege, Frank C P, Vormoor, H Josef, Hoving, Eelco W, van Noesel, Max M, Pieters, Rob, Kool, Marcel, Stumpf, Miriam, Blattner-Johnson, Mirjam, Balasubramanian, Gnana P, Van Tilburg, Cornelis M, Jones, Barbara C, Jones, David T W, Witt, Olaf, Pfister, Stefan M, Jongmans, Marjolijn C J, Kuiper, Roland P, de Krijger, Ronald R, Wijnen, Marc H W, den Boer, Monique L, Zwaan, C Michel, Kemmeren, Patrick, Koster, Jan, Tops, Bastiaan B J, Goemans, Bianca F, and Molenaar, Jan J
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- 2022
27. Preclinical Aortic Atherosclerosis in Adolescents With Chronic Disease
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CTI Boes, Onderzoek Vrouw Hart & Vaatziekten, Circulatory Health, Experimentele Afd. Cardiologie 1, Genetica Oper.Mang. Clinical Genetics, Cancer, Cluster B, Immuno/reuma ERN, Child Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Longziekten patientenzorg, Speerpunt Child Health, Onderzoek, MS Radiologie, Cardiologie patientenzorg, Ververs, Francesca A, Eikendal, Anouk L M, Kofink, Daniel, Nuboer, Roos, Westenberg, Jos J M, Hovenkamp, Gijs T, Kemps, Jitske J A, Coenen, Iris C J, Daems, Joëlle J N, Claus, Laura R, Ju, Yillie, Wulffraat, Nico M, van der Ent, Cornelis K, Monaco, Claudia, Boes, Marianne, Leiner, Tim, Grotenhuis, Heynric B, Schipper, Henk S, CTI Boes, Onderzoek Vrouw Hart & Vaatziekten, Circulatory Health, Experimentele Afd. Cardiologie 1, Genetica Oper.Mang. Clinical Genetics, Cancer, Cluster B, Immuno/reuma ERN, Child Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Longziekten patientenzorg, Speerpunt Child Health, Onderzoek, MS Radiologie, Cardiologie patientenzorg, Ververs, Francesca A, Eikendal, Anouk L M, Kofink, Daniel, Nuboer, Roos, Westenberg, Jos J M, Hovenkamp, Gijs T, Kemps, Jitske J A, Coenen, Iris C J, Daems, Joëlle J N, Claus, Laura R, Ju, Yillie, Wulffraat, Nico M, van der Ent, Cornelis K, Monaco, Claudia, Boes, Marianne, Leiner, Tim, Grotenhuis, Heynric B, and Schipper, Henk S
- Published
- 2022
28. Biallelic pathogenic variants in roundabout guidance receptor 1 associate with syndromic congenital anomalies of the kidney and urinary tract
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Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Klinische Genetica, Child Health, Genomics England Research Consortium, Genetica Oper.Mang. Clinical Genetics, Cancer, Genetica Klinische Genetica, Child Health, and Genomics England Research Consortium
- Published
- 2022
29. Development and Validation of a Prediction Model for Early Diagnosis of SCN1A-Related Epilepsies
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Genetica Klinische Genetica, Brain, Genetica Oper.Mang. Clinical Genetics, Child Health, Brunklaus, Andreas, Pérez-Palma, Eduardo, Ghanty, Ismael, Xinge, Ji, Brilstra, Eva, Ceulemans, Berten, Chemaly, Nicole, de Lange, Iris, Depienne, Christel, Guerrini, Renzo, Mei, Davide, Møller, Rikke S, Nabbout, Rima, Regan, Brigid M, Schneider, Amy L, Scheffer, Ingrid E, Schoonjans, An-Sofie, Symonds, Joseph D, Weckhuysen, Sarah, Kattan, Michael W, Zuberi, Sameer M, Lal, Dennis, Genetica Klinische Genetica, Brain, Genetica Oper.Mang. Clinical Genetics, Child Health, Brunklaus, Andreas, Pérez-Palma, Eduardo, Ghanty, Ismael, Xinge, Ji, Brilstra, Eva, Ceulemans, Berten, Chemaly, Nicole, de Lange, Iris, Depienne, Christel, Guerrini, Renzo, Mei, Davide, Møller, Rikke S, Nabbout, Rima, Regan, Brigid M, Schneider, Amy L, Scheffer, Ingrid E, Schoonjans, An-Sofie, Symonds, Joseph D, Weckhuysen, Sarah, Kattan, Michael W, Zuberi, Sameer M, and Lal, Dennis
- Published
- 2022
30. NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns
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Arts-assistenten Kinderen, Genetica Oper.Mang. Clinical Genetics, Child Health, Genetica Klinische Genetica, Brain, Genetica Groep Koeleman, Circulatory Health, Cancer, NEXMIF, Arts-assistenten Kinderen, Genetica Oper.Mang. Clinical Genetics, Child Health, Genetica Klinische Genetica, Brain, Genetica Groep Koeleman, Circulatory Health, Cancer, and NEXMIF
- Published
- 2021
31. Clinical Delineation and Localization to Chromosome 9p13.3–p12 of a Unique Dominant Disorder in Four Families: Hereditary Inclusion Body Myopathy, Paget Disease of Bone, and Frontotemporal Dementia
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Kovach, Margaret J., Waggoner, Brook, Leal, Suzanne M., Gelber, David, Khardori, Romesh, Levenstien, Mark A., Shanks, Christy A., Gregg, Gregory, Al-Lozi, Muhammad T., Miller, Timothy, Rakowicz, Wojtek, Lopate, Glenn, Florence, Juliane, Glosser, Guila, Simmons, Zachary, Morris, John C., Whyte, Michael P., Pestronk, Alan, and Kimonis, Virginia E.
- Published
- 2001
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32. Prenatal chromosome microarray: 'The UK experience'. A survey of reporting practices in UK genetic services (2012-2019).
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Patterson, Jenny, Wellesley, Diana, Morgan, Sian, Cilliers, Deirdre, Allen, Stephanie, Gardiner, Carol A, Fetal Genomics Steering Group, UK Clinical Genetics Lead Clinician Group, and UK Heads of Genetics Laboratory Group
- Abstract
Background: The value of chromosome microarray (CMA) in the prenatal detection of significant chromosome anomalies is well-established. To guide the introduction of this technique in routine clinical practice, the Joint Committee on Genomics in Medicine developed national UK guidelines for reporting prenatal CMA in 2015.Objective: To evaluate the UK experience of utilising prenatal CMA.Method: A 36-item survey was distributed to all UK clinical genetics services (n = 23) in March 2019 requesting information pertaining to experience since diagnostic testing commenced and current practice (March 2018 to March 2019).Results: Eighteen UK genetics services currently offer prenatal CMA. A total of 14,554 tests had been performed. A pathogenic copy number variant was identified in 7.8% of tests overall, though the diagnostic rate increased to 8.4% in the final year of the survey. Variants of uncertain significance (VUS) were reported in 0.7% of tests, and 'actionable' incidental findings in 0.12%.Conclusion: Diagnostic rate has improved over time, while reporting of VUS has decreased. Reviewing survey responses at a national level highlights variation in testing experience and practice, raising considerations both for future guideline development and implementation of other novel techniques including prenatal whole exome sequencing. [ABSTRACT FROM AUTHOR]- Published
- 2021
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33. Contributors
- Author
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Agarwal, H.C., Agrawal, Rupesh, Arora, Ritu, Bageja, Shaloo, Bansal, Yogeshwari, Baruha, Rituraj, Bhartiya, Shibal, Chakrabarti, Meena, Chaudhuri, Zia, Chauhan, Deepender, Chowdhury, Veena, Dada, Tanuj, Das, Ujjal Kumar, Dutta, Ranjan, Fogla, Rajesh, Garg, S.P., Ghosh, B., Goel, Ruchi, Goel, B.S., Gopal, Lingam, Gowtham, L., Grover, A.K., Grover, Apoorv, Gupta, A.K., Gupta, Roshmi, Gupta, Charu, Gupta, Promila, Gupta, Priyanka, Gupta, Ashish, Gupta, Vivek, Halder, Nabanita, Honavar, Santosh G., Ichhpujani, Parul, Jain, Parul, Joshi, Gunjan, Karna, Satya, Karna, Madhu, Kaushik, Sushmita, Koul, Archana, Krishna, V., Kumar, Atul, Malhotra, Manish, Mehrotra, Nitin, Mazumdar, Shahana, Mehta, Sachin, Mehta, Shubha, Moksha, Laxmi, Mutha, Vineet, Nagpal, Amit, Nath, Madhu, Namperumalsamy, P., Narain, Shishir, Natarajan, S., Raina, Usha K., Rathinam, S.R., Sharma, Namrata, Sharma, Pradeep, Shelat, Binita B., Shroff, Cyrus M., Shroff, Noshir M., Shukla, Pallavi, Singh, Sapna, Singh, Suraj Senjam, Sood, N.N., Sood, Devindra, Sridhar, Uma, Sridhar Rao, B., Sudhamathi, K., Taneja Mittal, Shilpa, Tewari, H.K., Vashist, Praveen, Vasavada, Abhay R., Velpandian, Thirumurthy, Venkatesh, Pradeep, and Verma, Lalit
- Published
- 2020
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34. Mutations in the human laminin ??2 ( LAMB2 ) gene and the associated phenotypic spectrum a
- Author
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Pediatric Nephrology, University Children's Hospital, Erlangen, Germany ; Howard Hughes Medical Institute and Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, Michican, Howard Hughes Medical Institute and Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, Michican, Institute of Human Genetics, University Hospital Erlangen, University of Erlangen-Nuremberg, Germany, Nephrology Unit, Pediatric Department, Mubarak Alkabeer Hospital, Kuwait, Department of Pediatrics, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates, NICU Oslo University Hospital, Oslo, Norway, Department of Pediatric Nephrology, Istanbul University, Cerrahpa??a Medical Faculty, Istanbul, Turkey, Leicester Royal Infirmary, Leicester, United Kingdom, Department of Pediatrics, University Hospital Motol, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic, Pediatric Nephrology, Great Ormond Street Hospital for Children, London, United Kingdom, Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea, Department of Neonatal Intensive Care, Medical University of Silesia, Katowice, Poland, D??partement de P??diatrie, H??pital Edouard-Herriot, Universit?? Claude-Bernard, Lyon, France, Pediatric Nephrology, University Children's Hospital, Erlangen, Germany, Paediatric Nephrology, Department of Paediatric Medicine, University of Cape Town, South Africa, Department of Clinical Genetics, Great Ormond Street Hospital for Children, Institute of Child Health, UCL, London, United Kingdom, and Department of Pediatrics, Academic Medical Center, UVA, Amsterdam, The Netherlands, Department of Pediatric Nephrology, H??pital Universitaire des Enfants, Reine Fabiola, Universit?? Libre de Bruxelles, Brussels, Belgium, Department of Gastroenterology and Nephrology, Orenburg Regional Children's Hospital, Orenburg, Russia, Kariminejad-Najmabadi Pathology and Genetics Center, Teheran, Iran, Pediatric Nephrology, University Hospital Hamburg???Eppendorf, Hamburg, Germany, University Children's Hospital, Munster, Germany, Department of Human Genetics, Cincinnati Children's Hospital, Cincinnato, Ohio, Department of Medical Genetics, University Medical Center Utrecht, The Netherlands, Inova Fairfax Hospital for Children, Falls Church, Virginia, Hospital Santa Maria, Lisbon, Portugal, Pediatric Nephrology, University Children's Hospital, University of Rostock, Germany, Service de Nephrologie Pediatrique, Hopital Necker???Enfants Malades, Paris, France, Emeritus professor of the University Children's Hospital Nancy, France, St. George's University of London, London, United Kingdom, Kapiolani Medical Specialists and Department of Pediatrics, John A. Burns School of Medicine, Honolulu, Hawaii, Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom, Nephrology, The Scientific Center of Children's Health, Moscow, Russia, Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University of Heidelberg, Germany, Department Pediatric & Adolescent Nephrology & Hypertension, Medical University Gdansk, Gdansk, Poland, Universit?? Paris Descartes, Inserm U574, and Assistance Publique-H??pitaux de Paris (AP-HP), D??partement de G??n??tique, H??pital Necker-Enfants Malades, Paris, France, Institute of Human Genetics, University Hospital Erlangen, University of Erlangen-Nuremberg, Germany ; Institute of Human Genetics, University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany ; Institute of Human Genetics, University Hospital Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany, Matejas, Verena, Hinkes, Bernward, Alkandari, Faisal, Al-Gazali, Lihadh, Annexstad, Ellen, Aytac, Mehmet B., Barrow, Margaret, Bl??hov??, Kveta, Bockenhauer, Detlef, Cheong, Hae Il, Maruniak-Chudek, Iwona, Cochat, Pierre, D??tsch, J??rg, Gajjar, Priya, Hennekam, Raoul C., Janssen, Fran??oise, Kagan, Mikhail, Kariminejad, Ariana, Kemper, Markus J., Koenig, Jens, Kogan, Jillene, Kroes, Hester Y., Kuwertz-Br??king, Eberhard, Lewanda, Amy F., Medeira, Ana, Muscheites, Jutta, Niaudet, Patrick, Pierson, Michel, Saggar, Anand, Seaver, Laurie, Suri, Mohnish, Tsygin, Alexey, W??hl, Elke, Zurowska, Aleksandra, Uebe, Steffen, Hildebrandt, Friedhelm, Antignac, Corinne, Zenker, Martin, Pediatric Nephrology, University Children's Hospital, Erlangen, Germany ; Howard Hughes Medical Institute and Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, Michican, Howard Hughes Medical Institute and Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, Michican, Institute of Human Genetics, University Hospital Erlangen, University of Erlangen-Nuremberg, Germany, Nephrology Unit, Pediatric Department, Mubarak Alkabeer Hospital, Kuwait, Department of Pediatrics, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates, NICU Oslo University Hospital, Oslo, Norway, Department of Pediatric Nephrology, Istanbul University, Cerrahpa??a Medical Faculty, Istanbul, Turkey, Leicester Royal Infirmary, Leicester, United Kingdom, Department of Pediatrics, University Hospital Motol, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic, Pediatric Nephrology, Great Ormond Street Hospital for Children, London, United Kingdom, Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea, Department of Neonatal Intensive Care, Medical University of Silesia, Katowice, Poland, D??partement de P??diatrie, H??pital Edouard-Herriot, Universit?? Claude-Bernard, Lyon, France, Pediatric Nephrology, University Children's Hospital, Erlangen, Germany, Paediatric Nephrology, Department of Paediatric Medicine, University of Cape Town, South Africa, Department of Clinical Genetics, Great Ormond Street Hospital for Children, Institute of Child Health, UCL, London, United Kingdom, and Department of Pediatrics, Academic Medical Center, UVA, Amsterdam, The Netherlands, Department of Pediatric Nephrology, H??pital Universitaire des Enfants, Reine Fabiola, Universit?? Libre de Bruxelles, Brussels, Belgium, Department of Gastroenterology and Nephrology, Orenburg Regional Children's Hospital, Orenburg, Russia, Kariminejad-Najmabadi Pathology and Genetics Center, Teheran, Iran, Pediatric Nephrology, University Hospital Hamburg???Eppendorf, Hamburg, Germany, University Children's Hospital, Munster, Germany, Department of Human Genetics, Cincinnati Children's Hospital, Cincinnato, Ohio, Department of Medical Genetics, University Medical Center Utrecht, The Netherlands, Inova Fairfax Hospital for Children, Falls Church, Virginia, Hospital Santa Maria, Lisbon, Portugal, Pediatric Nephrology, University Children's Hospital, University of Rostock, Germany, Service de Nephrologie Pediatrique, Hopital Necker???Enfants Malades, Paris, France, Emeritus professor of the University Children's Hospital Nancy, France, St. George's University of London, London, United Kingdom, Kapiolani Medical Specialists and Department of Pediatrics, John A. Burns School of Medicine, Honolulu, Hawaii, Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom, Nephrology, The Scientific Center of Children's Health, Moscow, Russia, Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University of Heidelberg, Germany, Department Pediatric & Adolescent Nephrology & Hypertension, Medical University Gdansk, Gdansk, Poland, Universit?? Paris Descartes, Inserm U574, and Assistance Publique-H??pitaux de Paris (AP-HP), D??partement de G??n??tique, H??pital Necker-Enfants Malades, Paris, France, Institute of Human Genetics, University Hospital Erlangen, University of Erlangen-Nuremberg, Germany ; Institute of Human Genetics, University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany ; Institute of Human Genetics, University Hospital Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany, Matejas, Verena, Hinkes, Bernward, Alkandari, Faisal, Al-Gazali, Lihadh, Annexstad, Ellen, Aytac, Mehmet B., Barrow, Margaret, Bl??hov??, Kveta, Bockenhauer, Detlef, Cheong, Hae Il, Maruniak-Chudek, Iwona, Cochat, Pierre, D??tsch, J??rg, Gajjar, Priya, Hennekam, Raoul C., Janssen, Fran??oise, Kagan, Mikhail, Kariminejad, Ariana, Kemper, Markus J., Koenig, Jens, Kogan, Jillene, Kroes, Hester Y., Kuwertz-Br??king, Eberhard, Lewanda, Amy F., Medeira, Ana, Muscheites, Jutta, Niaudet, Patrick, Pierson, Michel, Saggar, Anand, Seaver, Laurie, Suri, Mohnish, Tsygin, Alexey, W??hl, Elke, Zurowska, Aleksandra, Uebe, Steffen, Hildebrandt, Friedhelm, Antignac, Corinne, and Zenker, Martin
- Abstract
Mutations of LAMB2 typically cause autosomal recessive Pierson syndrome, a disorder characterized by congenital nephrotic syndrome, ocular and neurologic abnormalities, but may occasionally be associated with milder or oligosymptomatic disease variants. LAMB2 encodes the basement membrane protein laminin ??2, which is incorporated in specific heterotrimeric laminin isoforms and has an expression pattern corresponding to the pattern of organ manifestations in Pierson syndrome. Herein we review all previously reported and several novel LAMB2 mutations in relation to the associated phenotype in patients from 39 unrelated families. The majority of disease-causing LAMB2 mutations are truncating, consistent with the hypothesis that loss of laminin ??2 function is the molecular basis of Pierson syndrome. Although truncating mutations are distributed across the entire gene, missense mutations are clearly clustered in the N-terminal LN domain, which is important for intermolecular interactions. There is an association of missense mutations and small in frame deletions with a higher mean age at onset of renal disease and with absence of neurologic abnormalities, thus suggesting that at least some of these may represent hypomorphic alleles. Nevertheless, genotype alone does not appear to explain the full range of clinical variability, and therefore hitherto unidentified modifiers are likely to exist. Hum Mutat 31:992???1002, 2010. ?? 2010 Wiley-Liss, Inc.
- Published
- 2010
35. Prognosis for pregnancies with trisomy 16 confined to the placenta: A Danish cohort study.
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Grau Madsen, Sandra, Uldbjerg, Niels, Sunde, Lone, Becher, Naja, Danish Fetal Medicine Study Group, and Danish Clinical Genetics Study Group
- Abstract
Objective: To evaluate the risk of adverse pregnancy outcome when trisomy 16 confined to the placenta is diagnosed and to identify possible prognostic markers for adverse outcomes in these pregnancies.Method: Registered cases (n = 49) of trisomy 16 diagnosed prenatally in Denmark from 1990 to 2013 were included.Results: Twenty-five of the pregnancies intended to be continued had confined placental trisomy 16 mosaicism (CPM16). Adverse pregnancy outcome was seen in 17 CPM16 pregnancies (68%), ranging from mild small for gestational age (SGA) to fetal malformations and intrauterine demise. For cases ascertained by combined first trimester screening, the median concentration of pregnancy associated plasma protein A (PAPP-A) was 0.17 MoM (IQR: 0.11 MoM). Adverse pregnancy outcome showed a trend toward an association with a high frequency of trisomic cells. Eight children (32%) were born at term with a normal birth weight and no malformations.Conclusion: The risk of adverse pregnancy outcome in case of CPM16 is correlated to ascertainment by combined first trimester screening and tends to be associated with a high frequency of trisomic cells in the placenta. We recommend that variables including ascertainment, the frequency of trisomic cells, and the maternal serum concentration of PAPP-A are taken into consideration when evaluating the prognosis in CPM16 while acknowledging that these factors are strongly correlated. [ABSTRACT FROM AUTHOR]- Published
- 2018
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36. Assessment of copy number variations in the nebulin gene and other nemaline myopathy-causing genes
- Author
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Helsingin yliopisto, bio- ja ympäristötieteellinen tiedekunta, biotieteiden laitos, Helsingfors universitet, bio- och miljövetenskapliga fakulteten, biovetenskapliga institutionen, University of Helsinki, Faculty of Biological and Environmental Sciences, Department of Biosciences, Division of Genetics, The Folkhälsan Institute of Genetics and the Department of Medical and Clinical Genetics, Medicum, Kiiski, Kirsi, Helsingin yliopisto, bio- ja ympäristötieteellinen tiedekunta, biotieteiden laitos, Helsingfors universitet, bio- och miljövetenskapliga fakulteten, biovetenskapliga institutionen, University of Helsinki, Faculty of Biological and Environmental Sciences, Department of Biosciences, Division of Genetics, The Folkhälsan Institute of Genetics and the Department of Medical and Clinical Genetics, Medicum, and Kiiski, Kirsi
- Abstract
Nemaline myopathy (NM) and related disorders constitute a heterogeneous group of congenital myopathies. Mutations in the nebulin gene (NEB) are the main cause of the recessively inherited form. NEB is one of the largest genes in the human genome consisting of 249 kb of genomic sequence. NEB contains 183 exons and a 32 kb homologous triplicate region (TRI) where eight exons are repeated three times. The aims of this Doctoral Thesis study were to develop and implement into diagnostics new efficient variant analysis methods for NEB and other NM-causing genes. The first aim was to design and validate a custom copy number microarray targeting the NM-causing genes for the detection of copy number variations. MLPA (multiplex ligation-dependent probe amplification) and Sanger sequencing were also used. The second aim was to utilise whole-exome sequencing to search for novel disease-causing variants in the known NM genes and try to identify novel NM genes. Lastly, the aim was to collect more data in order to try to find genotype-phenotype correlations of NEB-caused NM. The design and validation of the NM-CGH microarray was successful. Of the total sample cohort of 356 NM families, 196 NM families were studied using the custom-made NM-CGH array. Nine different novel large causative variants were identified in ten NM families. The size of these variants varies greatly, covering only a part of one NEB exon on up to dozens of NEB exons (72bp - 133 kb). In addition, a novel recurrent variation of the NEB TRI region was identified in 13% of the NM families and in 10% of the studied 60 control samples. Deviations of one copy are suggested to be benign but gains of two or more copies might be pathogenic. One novel homozygous deletion was also identified in another NM gene, TPM3, in a patient with severe NM. Furthermore, ten samples were studied using exome sequencing, and for six of those samples, novel disease-causing variant(s) were identified. Two variants were identified in one, Nemaliinimyopatia (NM) ja samankaltaiset taudit on monimuotoinen tautiryhmä synnynnäisten myopatioiden joukossa. Nebuliini-geenin (NEB) mutaatiot ovat yleisin resessiivisen NM:n aiheuttaja, eli taudin ilmeneminen vaatii geenivirheen sekä isältä että äidiltä perityssä alleelissa. NEB on kooltaan 249 kb, eli yksi ihmisen suurimmista geeneistä. NEB sisältää 183 eksonia ja se kattaa myös toistojaksoja, kuten ns. triplikaatioalueen (TRI), jossa kahdeksan eksonia toistuu kolme kertaa. Väitöskirjatutkimuksen tarkoituksena oli kehittää ja ottaa diagnostiseen käyttöön uusia mutaatioanalyysimenetelmiä NEB-geeniä sekä muita NM-geenejä varten. Tavoitteena oli suunnitella ja validoida NM-geeneihin kohdennettu mikrosiru, jolla voidaan tutkia kopiolukuvariaatioita näistä geeneistä. Eksomisekvensointia hyödynnettiin tautia aiheuttavien varianttien löytämiseksi tunnetuista NM-geeneistä sekä uusista geeneistä. Tavoitteena oli lisäksi kerätä lisätietoa siitä mitkä nebuliinimutaatiot aiheuttavat mitäkin nemaliinimyopatian alatyyppiä. NM-CGH-mikrosirun kehittäminen sekä validointi onnistui hyvin. Koko 356 NM-perheen näytekohortista NM-CGH-sirulla tutkittiin 196 perhettä, joista tunnistettiin yhteensä yhdeksän uutta suurta tautia aiheuttavaa varianttia kymmenestä eri NM-perheestä. Näiden mutaatioiden koko vaihtelee suuresti, kattaen vain osan yhdestä NEB-geenin eksonista aina yli puoleen koko geenistä (72 bp 133 kb). Lisäksi osoitettiin että 13 % tutkituista NM-perheistä sekä 10 % tutkituista 60 kontrollinäytteestä sisältää NEB:n triplikaatio-alueen kopiolukuvariaation. Tutkimustulosten perusteella yhden kopioluvun lisäys tai vähenemä olisi harmitonta mutta mikäli ylimääräisiä kopioita on kaksi tai enemmän, se voisi olla tautia aiheuttavaa. Lisäksi tunnistettiin homotsygoottinen suuri deleetio toisesta tunnetusta NM-geenistä, TPM3. Eksomisekvensoinnilla löydettiin puolestaan toinen tai molemmat tautia aiheuttavat variantit kuudelle kymmenestä tutkitusta NM-potilaasta. Yhdessä NM-perheess
- Published
- 2015
37. Molecular genetics of X-linked cone-rod dystrophy and Åland Island eye disease
- Author
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Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Obstetrics and Gynecology, Department of Clinical Genetics, HUSLAB, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Department of Medical Genetics, University of Helsinki, Jalkanen, Reetta, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Obstetrics and Gynecology, Department of Clinical Genetics, HUSLAB, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Department of Medical Genetics, University of Helsinki, and Jalkanen, Reetta
- Abstract
Inherited retinal diseases are the most common cause of vision loss among the working population in Western countries. It is estimated that ~1 of the people worldwide suffer from vision loss due to inherited retinal diseases. The severity of these diseases varies from partial vision loss to total blindness, and at the moment no effective cure exists. To date, nearly 200 mapped loci, including 140 cloned genes for inherited retinal diseases have been identified. By a rough estimation 50% of the retinal dystrophy genes still await discovery. In this thesis we aimed to study the genetic background of two inherited retinal diseases, X-linked cone-rod dystrophy and Åland Island eye disease. X-linked cone-rod dystrophy (CORDX) is characterized by progressive loss of visual function in school age or early adulthood. Affected males show reduced visual acuity, photophobia, myopia, color vision defects, central scotomas, and variable changes in fundus. The disease is genetically heterogeneous and two disease loci, CORDX1 and CORDX2, were known prior to the present thesis work. CORDX1, located on Xp21.1-11.4, is caused by mutations in the RPGR gene. CORDX2 is located on Xq27-28 but the causative gene is still unknown. Åland Island eye disease (AIED), originally described in a family living in Åland Islands, is a congenital retinal disease characterized by decreased visual acuity, fundus hypopigmentation, nystagmus, astigmatism, red color vision defect, myopia, and defective night vision. AIED shares similarities with another retinal disease, congenital stationary night blindness (CSNB2). Mutations in the L-type calcium channel α1F-subunit gene, CACNA1F, are known to cause CSNB2, as well as AIED-like disease. The disease locus of the original AIED family maps to the same genetic interval as the CACNA1F gene, but efforts to reveal CACNA1F mutations in patients of the original AIED family have been unsuccessful. The specific aims of this study were to map the disease gene in a la, Perinnölliset verkkokalvorappeumat ovat suurin näkövammaisuuden aiheuttaja työikäisten keskuudessa teollistuneissa maissa. Retiniitikoita eli periytyvää verkkokalvon rappeumaa sairastavia ihmisiä arvioidaan olevan noin promille maailman väestöstä. Periytyvät verkkokalvorappeumat ovat itse asiassa suuri joukko sairauksia, joiden periytymismalli ja taudin kuva vaihtelevat suuresti. Näihin osittaiseen tai täydelliseen sokeuteen johtaviin tauteihin ei tunneta tehokasta hoitokeinoa. Vilkkaan geenitutkimuksen ansiosta viime vuosina on tunnistettu useita kymmeniä geenejä, joiden virheet johtavat verkkokalvorappeuman syntyyn. Tämän tutkimuksen tavoitteena oli selvittää kahden harvinaisen X-kromosomissa peittyvästi periytyvän verkkokalvorappeuman, tappi-sauvadystrofian ja Ahvenanmaan silmäsairauden, geneettistä taustaa. X-kromosomaalinen tappi-sauvadystrofia (CORDX) on etenevä, yleensä lapsuudessa alkava verkkokalvoa rappeuttava sairaus, joka ilmenee ainoastaan miehillä. Taudin tyypillisimpiä piirteitä ovat merkittävä näöntarkkuuden aleneminen, näkökentän puutokset, voimakas likinäköisyys ja värinäön häiriöt. Taudin kantajanaiset ovat useimmiten oireettomia. CORDX on geneettisesti monimuotoinen tauti ja taudin taustalla tiedetään olevan ainakin kahden eri geenin virheet. Ahvenanmaan silmäsairaus (AIED) kuvattiin ensimmäisen kerran vuonna 1964 yhden suomalaisen suvun miespotilailla. Taudin tyypillisimpiä piirteitä ovat alentunut näöntarkkuus, likinäköisyys, hajataitteisuus, silmävärve ja puutteellinen hämäränäkö. Alkuperäisen AIED-suvun lisäksi Suomessa ja ulkomailla on kuvattu perheitä, joiden potilailla on AIED:n kaltainen tauti (AIED-like). AIED-like potilaiden taudin taustalla on virheet solukalvon kalsiumkanavageenissä, CACNA1F. Alkuperäisen AIED-suvun tautigeeni on paikannettu X-kromosomiin samalle alueelle, jolla CACNA1F geeni sijaitsee, mutta geenitutkimuksissa ei ole löytynyt virheitä kyseisestä geenistä. Tutkimusaineistoomme kuului suuri suomalainen CORDX-suku sekä
- Published
- 2008
38. Direct Information to At-risk Relatives (DIRECT)
- Author
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Göteborg University, Lund University, Karolinska Institutet, and Anna Rosen, Principal investigator, MD, PhD, Specialist in Clinical genetics
- Published
- 2024
39. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations
- Author
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[ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, Rantala, Johanna, [ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, and Rantala, Johanna
- Abstract
To access publisher's full text version of this article click on the hyperlink below, The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.
40. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.
- Author
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Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain; Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain. 2Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. 3Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 4Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain. 5Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain. 6IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. 7Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. 8Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid, Spain. 9Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain. 10Oncogenetics Laboratory, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Institut de Recerca (VHIR), and Universitat Autonoma de Barcelona, Barcelona, Spain. 11Oncology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 12Molecular Diagnostics Laboratory IRRP, National Centre for Scientific Research Demokritos Aghia Paraskevi Attikis, Athens, Greece. 13Molecular Genetics Laboratory (Department of Biochemistry), Cruces Hospital Barakaldo, Bizkaia, Spain. 14Medical Oncology Service, Hospital Clínico Lozano Blesa, San Juan Bosco, Zaragoza, Spain. 15Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Canada. 16Department of Oncology, Lund University, Lund, Sweden. 17Department of Oncology, Karolinska University Hospital, Stockholm, Sweden. 18Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. 19Department of Oncology, Lund University Hospital, Lund, Sweden. 20Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. 21Center for Clinical Cancer Genet, Osorio, Ana, Milne, Roger L, Kuchenbaecker, Karoline, Vaclová, Tereza, Pita, Guillermo, Alonso, Rosario, Peterlongo, Paolo, Blanco, Ignacio, de la Hoya, Miguel, Duran, Mercedes, Díez, Orland, Mai, Phuong L, Neuhausen, Susan L, Lejbkowicz, Flavio, Ottini, Laura, Lee, Andrew, Buys, Saundra S, Thomassen, Mads, Zaffaroni, Daniela, Andrulis, Irene, Benitez, Javier, Schmutzler, Rita Katharina, Eccles, Diana, Swe-Brca, Platte, Radka, Hodgson, Shirley, Tischkowitz, Marc, Meindl, Alfons, van Deurzen, Carolien H M, Nathanson, Katherine, Donaldson, Alan, Varon-Mateeva, Raymonda, Teulé, Alex, Walsh, Christine, Poppe, Bruce, Ditsch, Nina, Arver, Brita, Morrison, Patrick, Plendl, Hans Jörg, Sutter, Christian, Rantala, Johanna, Johannsson, Oskar Th, Janavicius, Ramunas, Wappenschmidt, Barbara, Stoppa-Lyonnet, Dominique, Brewster, Wendy, Olswold, Curtis, Ding, Yuan Chun, Rookus, Matti A, Lester, Jenny, John, Esther M, Gehrig, Andrea, Herzog, Josef, Lalloo, Fiona, Kauff, Noah, Whittemore, Alice S, Rau-Murthy, Rohini, Weeman, Kisa, Claes, Kathleen, Rutherford, Thomas, Gómez Garcia, Encarna B, Berger, Andreas, Bonanni, Bernardo, Hebon, Hansen, Thomas V O, Rhiem, Kerstin, Jønson, Lars, Wakeley, Katie, Garber, Judy, Foo, Claire, Toland, Amanda Ewart, Ejlertsen, Bent, Pedersen, Inge Sokilde, Ellis, Steve, van Os, Theo A M, Collée, J Margriet, van der Luijt, Rob B, Lubinski, Jan, Simard, Jacques, Izatt, Louise, Teixeira, Manuel R, Mariette, Frederique, Piedmonte, Marion, Volorio, Sara, Hoogerbrugge, Nicoline, Porteous, Mary, Mazoyer, Sylvie, Wang-Gohrke, Shan, Martínez-Bouzas, Cristina, Viel, Alessandra, Soucy, Penny, Side, Lucy, Olah, Edith, Jaworska-Bieniek, Katarzyna, Maugard, Christine, Vijai, Joseph, Beattie, Mary S, Godwin, Andrew K, Investigators, Kconfab, Geschwantler Kaulich, Daphne, Eeles, Ros, van der Kolk, Lizet, Adlard, Julian, Durda, Katarzyna, Steinemann, Doris, Nevanlinna, Heli, Douglas, Fiona, Lázaro, Conxi, Davidson, Rosemarie, Engel, Christoph, Robson, Mark, Preisler-Adams, Sabine, Healey, Sue, Zhang, Liying, Fink-Retter, Anneliese, Mulligan, Anna Marie, Terry, Mary B, Damiola, Francesca, Tea, Muy-Kheng, Friedman, Eitan, Tucker, Kathy, Couch, Fergus J, Glendon, Gord, Kast, Karin, Pfeiler, Georg, Bojesen, Anders, Sunde, Lone, Ramón Y Cajal, Teresa, Moreno, Leticia Thais, Aittomäki, Kristiina, Shimon, Shani Paluch, Loman, Niklas, Scuvera, Giulietta, de Lange, J L, Rebbeck, Timothy R, Konstantopoulou, Irene, Backes, Floor, Laitman, Yael, Andrés Conejero, Raquel, McGuffog, Lesley, Rodríguez, Gustavo, Radice, Paolo, Devilee, Peter, Chenevix-Trench, Georgia, Olopade, Olufunmilayo I, Daly, Mary B, Evans, Gareth, Menéndez, Mireia, Dorfling, Cecilia M, Meijers-Heijboer, Hanne E J, van der Hout, A H, Ehrencrona, Hans, Montagna, Marco, Phelan, Catherine M, Cook, Jackie, van Asperen, Christi J, Brewer, Carole, Tognazzo, Silvia, Arun, Banu K, Hopper, John, Gerdes, Anne-Marie, Kennedy, John, Guidugli, Lucia, Manoukian, Siranoush, Jakubowska, Anna, Antoniou, Antonis C, Cybulski, Cezary, Southey, Melissa, Singer, Christian F, Easton, Douglas F, Arnold, Norbert, Gronwald, Jacek, Niederacher, Dieter, Rappaport, Christine, van Rensburg, Elizabeth J, Herráez, Belén, Weitzel, Jeffrey N, Varesco, Liliana, Sinilnikova, Olga M, Greene, Mark H, Frost, Debra, Lindor, Noralane, Karlan, Beth Y, Slager, Susan, Infante, Mar, Kruse, Torben A, Domchek, Susan M, Barrowdale, Daniel, Steele, Linda, Szabo, Csilla I, Papi, Laura, Jensen, Uffe Birk, Peissel, Bernard, Tibiletti, Maria Grazia, Yannoukakos, Drakoulis, Cole, Trevor, Caldés, Trinidad, Offit, Kenneth, Fineberg, Elena, Walker, Lisa, Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain; Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain. 2Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. 3Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 4Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain. 5Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain. 6IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. 7Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. 8Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid, Spain. 9Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain. 10Oncogenetics Laboratory, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Institut de Recerca (VHIR), and Universitat Autonoma de Barcelona, Barcelona, Spain. 11Oncology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 12Molecular Diagnostics Laboratory IRRP, National Centre for Scientific Research Demokritos Aghia Paraskevi Attikis, Athens, Greece. 13Molecular Genetics Laboratory (Department of Biochemistry), Cruces Hospital Barakaldo, Bizkaia, Spain. 14Medical Oncology Service, Hospital Clínico Lozano Blesa, San Juan Bosco, Zaragoza, Spain. 15Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Canada. 16Department of Oncology, Lund University, Lund, Sweden. 17Department of Oncology, Karolinska University Hospital, Stockholm, Sweden. 18Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. 19Department of Oncology, Lund University Hospital, Lund, Sweden. 20Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. 21Center for Clinical Cancer Genet, Osorio, Ana, Milne, Roger L, Kuchenbaecker, Karoline, Vaclová, Tereza, Pita, Guillermo, Alonso, Rosario, Peterlongo, Paolo, Blanco, Ignacio, de la Hoya, Miguel, Duran, Mercedes, Díez, Orland, Mai, Phuong L, Neuhausen, Susan L, Lejbkowicz, Flavio, Ottini, Laura, Lee, Andrew, Buys, Saundra S, Thomassen, Mads, Zaffaroni, Daniela, Andrulis, Irene, Benitez, Javier, Schmutzler, Rita Katharina, Eccles, Diana, Swe-Brca, Platte, Radka, Hodgson, Shirley, Tischkowitz, Marc, Meindl, Alfons, van Deurzen, Carolien H M, Nathanson, Katherine, Donaldson, Alan, Varon-Mateeva, Raymonda, Teulé, Alex, Walsh, Christine, Poppe, Bruce, Ditsch, Nina, Arver, Brita, Morrison, Patrick, Plendl, Hans Jörg, Sutter, Christian, Rantala, Johanna, Johannsson, Oskar Th, Janavicius, Ramunas, Wappenschmidt, Barbara, Stoppa-Lyonnet, Dominique, Brewster, Wendy, Olswold, Curtis, Ding, Yuan Chun, Rookus, Matti A, Lester, Jenny, John, Esther M, Gehrig, Andrea, Herzog, Josef, Lalloo, Fiona, Kauff, Noah, Whittemore, Alice S, Rau-Murthy, Rohini, Weeman, Kisa, Claes, Kathleen, Rutherford, Thomas, Gómez Garcia, Encarna B, Berger, Andreas, Bonanni, Bernardo, Hebon, Hansen, Thomas V O, Rhiem, Kerstin, Jønson, Lars, Wakeley, Katie, Garber, Judy, Foo, Claire, Toland, Amanda Ewart, Ejlertsen, Bent, Pedersen, Inge Sokilde, Ellis, Steve, van Os, Theo A M, Collée, J Margriet, van der Luijt, Rob B, Lubinski, Jan, Simard, Jacques, Izatt, Louise, Teixeira, Manuel R, Mariette, Frederique, Piedmonte, Marion, Volorio, Sara, Hoogerbrugge, Nicoline, Porteous, Mary, Mazoyer, Sylvie, Wang-Gohrke, Shan, Martínez-Bouzas, Cristina, Viel, Alessandra, Soucy, Penny, Side, Lucy, Olah, Edith, Jaworska-Bieniek, Katarzyna, Maugard, Christine, Vijai, Joseph, Beattie, Mary S, Godwin, Andrew K, Investigators, Kconfab, Geschwantler Kaulich, Daphne, Eeles, Ros, van der Kolk, Lizet, Adlard, Julian, Durda, Katarzyna, Steinemann, Doris, Nevanlinna, Heli, Douglas, Fiona, Lázaro, Conxi, Davidson, Rosemarie, Engel, Christoph, Robson, Mark, Preisler-Adams, Sabine, Healey, Sue, Zhang, Liying, Fink-Retter, Anneliese, Mulligan, Anna Marie, Terry, Mary B, Damiola, Francesca, Tea, Muy-Kheng, Friedman, Eitan, Tucker, Kathy, Couch, Fergus J, Glendon, Gord, Kast, Karin, Pfeiler, Georg, Bojesen, Anders, Sunde, Lone, Ramón Y Cajal, Teresa, Moreno, Leticia Thais, Aittomäki, Kristiina, Shimon, Shani Paluch, Loman, Niklas, Scuvera, Giulietta, de Lange, J L, Rebbeck, Timothy R, Konstantopoulou, Irene, Backes, Floor, Laitman, Yael, Andrés Conejero, Raquel, McGuffog, Lesley, Rodríguez, Gustavo, Radice, Paolo, Devilee, Peter, Chenevix-Trench, Georgia, Olopade, Olufunmilayo I, Daly, Mary B, Evans, Gareth, Menéndez, Mireia, Dorfling, Cecilia M, Meijers-Heijboer, Hanne E J, van der Hout, A H, Ehrencrona, Hans, Montagna, Marco, Phelan, Catherine M, Cook, Jackie, van Asperen, Christi J, Brewer, Carole, Tognazzo, Silvia, Arun, Banu K, Hopper, John, Gerdes, Anne-Marie, Kennedy, John, Guidugli, Lucia, Manoukian, Siranoush, Jakubowska, Anna, Antoniou, Antonis C, Cybulski, Cezary, Southey, Melissa, Singer, Christian F, Easton, Douglas F, Arnold, Norbert, Gronwald, Jacek, Niederacher, Dieter, Rappaport, Christine, van Rensburg, Elizabeth J, Herráez, Belén, Weitzel, Jeffrey N, Varesco, Liliana, Sinilnikova, Olga M, Greene, Mark H, Frost, Debra, Lindor, Noralane, Karlan, Beth Y, Slager, Susan, Infante, Mar, Kruse, Torben A, Domchek, Susan M, Barrowdale, Daniel, Steele, Linda, Szabo, Csilla I, Papi, Laura, Jensen, Uffe Birk, Peissel, Bernard, Tibiletti, Maria Grazia, Yannoukakos, Drakoulis, Cole, Trevor, Caldés, Trinidad, Offit, Kenneth, Fineberg, Elena, and Walker, Lisa
- Abstract
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access., Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
41. Heart Disease Characterization and Myocardial Strain Analysis in Patients with PACS1 Neurodevelopmental Disorder
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Latorre-Pellicer, Ana, Trujillano Lidón, Laura, del Rincón de la Villa, Julia, Peña-Marco, Mónica, Gil Salvador, Marta, Lucia Campos, Cristina, Institut Català de la Salut, [Latorre-Pellicer A, Del Rincón J, Peña-Marco M, Gil-Salvador M, Lucia-Campos C] Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, Universidad de Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain. [Trujillano L] Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, Universidad de Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain. Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Cardiovascular Diseases::Heart Diseases [DISEASES] ,trastornos mentales::trastornos del desarrollo neurológico [PSIQUIATRÍA Y PSICOLOGÍA] ,Hipertensió ,Cardiovascular Diseases::Vascular Diseases::Hypertension [DISEASES] ,Malalties mentals ,enfermedades cardiovasculares::enfermedades cardíacas [ENFERMEDADES] ,Cor - Malalties ,enfermedades cardiovasculares::enfermedades vasculares::hipertensión [ENFERMEDADES] ,Mental Disorders::Neurodevelopmental Disorders [PSYCHIATRY AND PSYCHOLOGY] - Abstract
Neurodevelopmental disorder; Congenital heart disease; Myocardial strain analysis Trastorn del neurodesenvolupament; Malaltia cardíaca congènita; Anàlisi de la tensió miocàrdica Trastorno del neurodesarrollo; Enfermedad cardíaca congénita; Análisis de la tensión miocárdica Background: PACS1 neurodevelopmental disorder (PACS1-NDD) (MIM# 615009) is a rare autosomal dominant disease characterized by neurodevelopmental delay, dysmorphic facial features, and congenital malformations. Heart disease (HD) is frequently present in individuals with PACS1-NDD, but a compressive review of these anomalies and an evaluation of cardiac function in a cohort of patients are lacking. Methods: (i) Cardiac evaluation in 11 PACS1-NDD patients was conducted using conventional echocardiography. (ii) Heart function was assessed by tissue Doppler imaging, and two-dimensional speckle tracking was performed in seven patients and matched controls. (iii) This systematic review focused on determining HD prevalence in individuals with PACS1-NDD. Results: In our cohort, 7 of 11 patients presented HD. (Among them, three cases of ascending aortic dilatation (AAD) were detected and one mitral valve prolapse (MVP).) None of the patients showed echocardiographic pathological values, and the left global longitudinal strain was not significantly different between patients and controls (patients −24.26 ± 5.89% vs. controls −20.19 ± 1.75%, p = 0.3176). In the literature review, almost 42% (42/100) of individuals with PACS1-NDD reportedly experienced HD. Septal defects were the most common malformation, followed by patent ductus arteriosus. Conclusions: Our results show a high prevalence of HD in PACS1-NDD patients; in this way, AAD and MVP are reported for the first time in this syndrome. Furthermore, a detailed cardiac function evaluation in our cohort did not reveal evidence of cardiac dysfunction in individuals with PACS1-NDD. Cardiology evaluation should be included for all individuals with Schuurs-Hoeijmakers syndrome. This work was supported by the Spanish Ministry of Health-ISCIII Fondo de Investigación Sanitaria (FIS) (Ref. PI19/01860, to F.J.R. and J.P.) and the Diputación General de Aragón-FEDER: European Social Fund (Grupo de Referencia B32_17R/B32_20R, to J.P.). A.L.-P. was supported by a Miguel Servet ISC-III Research Contract (CP22/00105), and M.G.-S. and C.L.-C. were, respectively, supported by predoctoral fellowships from the Diputación General de Aragón and the Spanish Ministry of Health-ISCIII (FI20/00290).
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- 2023
42. Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing
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Schuurman, L.V., Sistermans, E.A., Opstal, D. van, Henneman, L., Bekker, M.N., Bax, C.J., Pieters, M.J., Bouman, K., Munnik, S. de, Hollander, N.S. den, Diderich, K.E.M., Faas, B.H.W., Feenstra, I., Go, A.T.J.I., Hoffer, M.J.V., Joosten, M., Komdeur, F.L., Lichtenbelt, K.D., Lombardi, M.P., Polak, M.G., Jehee, F.S., Schuring-Blom, H., Stevens, S.J.C., Srebniak, M.I., Suijkerbuijk, R.F., Tan-Sindhunata, G.M., Meij, K.R.M. van der, Maarle, M.C. van, Vernimmen, V., Zelderen-Bhola, S.L. van, Ravesteyn, N.T. van, Knapen, M.F.C.M., Macville, M.V.E., Galjaard, R.J.H., Dutch NIPT Consortium, Human genetics, Amsterdam Reproduction & Development (AR&D), Obstetrics and gynaecology, Pathology, Rehabilitation medicine, APH - Quality of Care, Obstetrics and Gynaecology, Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, Public Health, Clinical Genetics, Obstetrics & Gynecology, Department of Psychology, Education and Child Studies, Clinical genetics, Amsterdam Reproduction & Development, Emergency Medicine, Research Methods and Techniques, RS: GROW - R4 - Reproductive and Perinatal Medicine, Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), MUMC+: DA KG Lab Specialisten (9), MUMC+: DA KG Lab Centraal Lab (9), MUMC+: DA KG Polikliniek (9), and MUMC+: DA KG AIOS (9)
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Placenta ,Trisomy ,first tier test ,Cohort Studies ,genome-wide ,Pregnancy ,Prenatal Diagnosis/methods ,Prenatal Diagnosis ,Genetics ,Humans ,cfDNA ,Genetics (clinical) ,confined placental mosaicism ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Mosaicism ,Other Research Radboud Institute for Health Sciences [Radboudumc 0] ,NIPS ,fetal trisomy ,PREECLAMPSIA ,common trisomies ,prenatal screening ,CELL-FREE DNA ,Female ,NIPT ,Follow-Up Studies ,rare autosomal trisomies - Abstract
Contains fulltext : 251979.pdf (Publisher’s version ) (Open Access) In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight
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- 2022
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43. Changes in opinions about human germline gene editing as a result of the Dutch DNA-dialogue project
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Diewertje Houtman, Boy Vijlbrief, Marike Polak, Jacqueline Pot, Petra Verhoef, Martina Cornel, Sam Riedijk, Clinical genetics, APH - Personalized Medicine, APH - Quality of Care, Amsterdam Reproduction & Development, Human genetics, Amsterdam Reproduction & Development (AR&D), Clinical Genetics, Department of Life Sciences, and Research Methods and Techniques
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SDG 3 - Good Health and Well-being ,Genetics ,Genetics (clinical) - Abstract
Public engagement for Human Germline Genome Editing (HGGE) has often been called for, for example by the WHO. However, the impact of public engagement remains largely unknown. This study reports on public engagement outcomes in the context of a public dialogue project about HGGE in the Netherlands; the DNA-dialogue. The aim was to inquire opinions and opinion change regarding HGGE. A questionnaire was distributed on a national level (n = 2381) and a dialogue level (n = 414). The results indicate that the majority of the Dutch population agrees with the use of HGGE to prevent severe genetic diseases (68.6%), unlike the use to protect against infectious diseases (39.7%), or for enhancement (8.5%). No indications of change in these acceptance rates as a result of dialogue participation were found. The results did provide a tentative indication that participation in dialogue may lead to less negative opinions about HGGE (χ2(1) = 5.14, p = 0.023, OR = 0.56, 95% CI [0.34, 0.93]). While it was not a goal of the project to make people more accepting towards HGGE, this might be the effect of exposure to opinions that are less often heard in the global debate. We conclude that dialogue may lead to different outcomes for different people, depending on their characteristics and their entrance attitude, but does not appear to systematically direct people towards a certain opinion. The self-reported, impacts of dialogue participation included no impact, strengthening of opinion, enabling of forming a first opinion, more insight into the potential implications of HGGE, and a better understanding of other people’s perspectives.
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- 2022
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44. Biallelic ADAM22 pathogenic variants cause progressive encephalopathy and infantile-onset refractory epilepsy
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Marieke M van der Knoop, Reza Maroofian, Yuko Fukata, Yvette van Ierland, Ehsan G Karimiani, Anna Elina Lehesjoki, Mikko Muona, Anders Paetau, Yuri Miyazaki, Yoko Hirano, Laila Selim, Marina de França, Rodrigo Ambrosio Fock, Christian Beetz, Claudia A L Ruivenkamp, Alison J Eaton, Francois D Morneau-Jacob, Lena Sagi-Dain, Lilach Shemer-Meiri, Amir Peleg, Jumana Haddad-Halloun, Daan J Kamphuis, Cacha M P C D Peeters-Scholte, Semra Hiz Kurul, Rita Horvath, Hanns Lochmüller, David Murphy, Stephan Waldmüller, Stephanie Spranger, David Overberg, Alison M Muir, Aboulfazl Rad, Barbara Vona, Firdous Abdulwahad, Sateesh Maddirevula, Inna S Povolotskaya, Victoria Y Voinova, Vykuntaraju K Gowda, Varunvenkat M Srinivasan, Fowzan S Alkuraya, Heather C Mefford, Majid Alfadhel, Tobias B Haack, Pasquale Striano, Mariasavina Severino, Masaki Fukata, Yvonne Hilhorst-Hofstee, Henry Houlden, Neurology, Clinical Genetics, Department of Medical and Clinical Genetics, University of Helsinki, Medicum, HUSLAB, and Department of Pathology
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Brain Diseases ,Drug Resistant Epilepsy ,CYSTIC-FIBROSIS ,GENES ,LEUCINE-RICH ,3112 Neurosciences ,ADAM22 ,Intracellular Signaling Peptides and Proteins ,PROTEIN ,Nerve Tissue Proteins ,PHENOTYPE ,3124 Neurology and psychiatry ,refractory seizures ,ADAM Proteins ,Humans ,SEIZURES ,LGI1 ,LIMBIC ENCEPHALITIS ,Neurology (clinical) ,developmental and epileptic encephalopathy ,Atrophy ,Epilèpsia en els infants ,Disks Large Homolog 4 Protein - Abstract
Data de publicació electrònica: 04-04-2022 Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harboring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available. Additionally, we provide follow-up data from two previously reported cases. All affected individuals exhibited infantile-onset, treatment-resistant epilepsy. Additional clinical features included moderate to profound global developmental delay/intellectual disability (20/20), hypotonia (12/20), delayed motor development (19/20). Brain MRI findings included cerebral atrophy (13/20), supported by post-mortem histological examination in patient-derived brain tissue, cerebellar vermis atrophy (5/20), and callosal hypoplasia (4/20). Functional studies in transfected cell lines confirmed the deleteriousness of all identified variants and indicated at least three distinct pathological mechanisms: defective cell membrane expression (1), impaired LGI1-binding (2), and/or impaired interaction with the postsynaptic density protein PSD-95 (3). We reveal novel clinical and molecular hallmarks of ADAM22 deficiency and provide knowledge that might inform clinical management and early diagnostics. Funding: most families were collected as part of the SYNaPS Study Group collaboration funded by the Wellcome Trust and strategic award (Synaptopathies) funding (WT093205 MA and WT104033AIA). This study was also supported by JSPS/MEXT KAKENHI (Grants 19H03331, 19K22439 and 21K19390 to Y.F., Grant 19K16269 to Y.M., and Grants 20H00459 and 20H04915 to M.F.) and Japan Agency for Medical Research and Development (21wm0525022h0001 to Y.F.); intramural funding (fortüne) from the University of Tübingen (Grant 2545-1-0) and the Ministry of Science, Research and Art Baden-Württemberg to B.V. P.S. contributed to this work within the framework of the DINOGMI Department of Excellence of MIUR 2018-2022 (legge 232 del 2016). T.B.H. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 418081722, 433158657. I.S.P., V.Y.V. are supported by the Government Assignment of the Russian Ministry of Health (#121061500066-2). HL receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C), the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279). S.H. is funded by TUBITAK (Turkish Scientific and Technological Research Council) Project number 216S771. R.H. is a Wellcome Trust Investigator (109915/Z/15/Z), who received support from the Medical Research Council (UK) (MR/N025431/1 and MR/V009346/1), the European Research Council (309548), the Newton Fund (UK/Turkey, MR/N027302/1), the Addenbrookes Charitable Trust (G100142), the Evelyn Trust, the Stoneygate Trust, the Lily Foundation and an MRC strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) MR/S005021/1. This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014)
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- 2022
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45. Extending the phenotypes associated with <scp> TRIO </scp> gene variants in a cohort of 25 patients and review of the literature
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Gabriella Gazdagh, David Hunt, Anna Maria Cueto Gonzalez, Monserrat Pons Rodriguez, Ayeshah Chaudhry, Marcos Madruga, Fleur Vansenne, Deborah Shears, Aurore Curie, Eva‐Lena Stattin, Britt‐Marie Anderlid, Slavica Trajkova, Elena Sukarova Angelovska, Catherine McWilliam, Philip R. Wyatt, Mary O'Driscoll, Giles Atton, Anke K. Bergman, Pia Zacher, Leena D. Mewasingh, Antonio Gonzalez‐Meneses López, Olga Alonso‐Luengo, Htoo A. Wai, Ottilie Rohde, Pauline Boiroux, Anne Debant, Susanne Schmidt, Diana Baralle, Institut Català de la Salut, [Gazdagh G] Wessex Clinical Genetics Service, Princess Anne Hospital, University Hospital Southampton NHS Trust, Southampton, UK. Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. [Hunt D] Wessex Clinical Genetics Service, Princess Anne Hospital, University Hospital Southampton NHS Trust, Southampton, UK. [Cueto Gonzalez AM] Servei de Genètica Clínica i Molecular, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Pons Rodriguez M] Hospital Universitari Son Espases, Palma, Illes Balears, Spain. [Chaudhry A] Department of Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, Ontario, Canada. Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. [Madruga M] Hospital Viamed Santa Angela De la Cruz, Sevilla, Spain, and Vall d'Hebron Barcelona Hospital Campus
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enfermedades del sistema nervioso::malformaciones del sistema nervioso [ENFERMEDADES] ,phenotype ,Nervous System Diseases::Nervous System Malformations [DISEASES] ,fenómenos genéticos::variación genética::mutación::mutación de sentido erróneo [FENÓMENOS Y PROCESOS] ,macrocephaly ,Sistema nerviós - Malalties - Aspectes genètics ,Fenotip ,spectrin ,Anomalies cromosòmiques ,GEFD ,Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES] ,Genetics ,TRIO gene ,Malformacions ,Genetic Phenomena::Genetic Variation::Mutation::Mutation, Missense [PHENOMENA AND PROCESSES] ,microcephaly ,Medical Genetics ,fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS] ,Genetics (clinical) ,Medicinsk genetik - Abstract
TRIO gene; Macrocephaly; Phenotype Gen TRIO; Macrocefàlia; Fenotip Gen TRIO; Macrocefalia; Fenotipo The TRIO gene encodes a rho guanine exchange factor, the function of which is to exchange GDP to GTP, and hence to activate Rho GTPases, and has been described to impact neurodevelopment. Specific genotype-to-phenotype correlations have been established previously describing striking differentiating features seen in variants located in specific domains of the TRIO gene that are associated with opposite effects on RAC1 activity. Currently, 32 cases with a TRIO gene alteration have been published in the medical literature. Here, we report an additional 25, previously unreported individuals who possess heterozygous TRIO variants and we review the literature. In addition, functional studies were performed on the c.4394A > G (N1465S) and c.6244-2A > G TRIO variants to provide evidence for their pathogenicity. Variants reported by the current study include missense variants, truncating nonsense variants, and an intragenic deletion. Clinical features were previously described and included developmental delay, learning difficulties, microcephaly, macrocephaly, seizures, behavioral issues (aggression, stereotypies), skeletal problems including short, tapering fingers and scoliosis, dental problems (overcrowding/delayed eruption), and variable facial features. Here, we report clinical features that have not been described previously, including specific structural brain malformations such as abnormalities of the corpus callosum and ventriculomegaly, additional psychological and dental issues along with a more recognizable facial gestalt linked to the specific domains of the TRIO gene and the effect of the variant upon the function of the encoded protein. This current study further strengthens the genotype-to-phenotype correlation that was previously established and extends the range of phenotypes to include structural brain abnormalities, additional skeletal, dental, and psychiatric issues. This work was supported by grants from the Agence Nationale de la Recherche to Anne Debant (ANR-2019 TRIOTISM). Diana Baralle is supported by National Institute for Health Research (NIHR) (RP-2016-07-011) research professorship.
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- 2023
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46. Effects of chemotherapy on contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers
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Akdeniz, D., Barele, M. van, Heemskerk-Gerritsen, B.A.M., Steyerberg, E.W., Hauptmann, M., Beek, I. van de, Engelen, K. van, Wevers, M.R., Garcia, E.B.G., Ausems, M.G.E.M., Berger, L.P.V., Asperen, C.J. van, Adank, M.A., Collee, M.J., Stommel-Jenner, D.J., Jager, A., Schmidt, M.K., Hooning, M.J., HEBON Investigators, Medical Oncology, Public Health, Clinical Genetics, Faculteit Medische Wetenschappen/UMCG, Clinical genetics, Epidemiology and Data Science, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), and Klinische Genetica
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PALGA, The nationwide network and registry of histo- and cytopathology in The Netherlands ,Heterozygote ,Secondary ,endocrine system diseases ,Breast Neoplasms ,MUTATION CARRIERS ,HEBON, Hereditary Breast and Ovarian cancer research Netherlands ,Cohort Studies ,NEOADJUVANT CHEMOTHERAPY ,All institutes and research themes of the Radboud University Medical Center ,Breast cancer ,PROGNOSTIC-FACTORS ,SDG 3 - Good Health and Well-being ,Humans ,Chemotherapy ,Genetic Predisposition to Disease ,skin and connective tissue diseases ,RC254-282 ,BRCA2 Protein ,PBC, primary breast cancer ,BRCA1 Protein ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,General Medicine ,BRCA1 ,HR, hazard ratio ,BRCA2 ,CI, confidence interval ,GRADE ,Risk factors ,Chemotherapy, Adjuvant ,Mutation ,SURVIVAL ,Surgery ,Original Article ,CBC, contralateral breast cancer ,Female ,CMF, cyclophosphamide, methotrexate, 5-fluorouracil ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,NCR, Netherlands Cancer Registry - Abstract
Aim BRCA1/2 mutation carriers with primary breast cancer (PBC) are at high risk of contralateral breast cancer (CBC). In a nationwide cohort, we investigated the effects of chemotherapeutic agents given for PBC on CBC risk separately in BRCA1 and BRCA2 mutation carriers. Patients and methods BRCA1 or BRCA2 mutation carriers with an invasive PBC diagnosis from 1990 to 2017 were selected from a Dutch cohort. We estimated cumulative CBC incidence using competing risks analysis. Hazard ratios (HR) for the effect of neo-adjuvant or adjuvant chemotherapy and different chemotherapeutic agents on CBC risk were estimated using Cox regression. Results We included 1090 BRCA1 and 568 BRCA2 mutation carriers; median follow-up was 8.9 and 8.4 years, respectively. Ten-year cumulative CBC incidence for treatment with and without chemotherapy was 6.7% [95%CI: 5.1–8.6] and 16.7% [95%CI: 10.8–23.7] in BRCA1 and 4.8% [95%CI: 2.7–7.8] and 16.0% [95%CI: 9.3–24.4] in BRCA2 mutation carriers, respectively. Chemotherapy was associated with reduced CBC risk in BRCA1 (multivariable HR: 0.46, 95%CI: 0.29–0.74); a similar trend was observed in BRCA2 mutation carriers (HR: 0.63, 95%CI: 0.29–1.39). In BRCA1, risk reduction was most pronounced in the first 5 years (HR: 0.32, 95%CI: 0.17–0.61). Anthracyclines and the combination of anthracyclines with taxanes were associated with substantial CBC risk reduction in BRCA1 carriers (HR: 0.34, 95%CI: 0.17–0.68 and HR: 0.22, 95%CI: 0.08–0.62, respectively). Conclusion Risk-reducing effects of chemotherapy are substantial for at least 5 years and may be used in personalised CBC risk prediction in any case for BRCA1 mutation carriers., Highlights • Contralateral breast cancer (CBC) risk is high in BRCA1/2 mutation carriers. • Chemotherapy for primary breast cancer results in decreased CBC risk in BRCA1. • Anthracyclines with/without taxanes show the largest CBC risk reduction in BRCA1. • For BRCA2 similar trends are observed as in BRCA1 mutation carriers. • Chemotherapy must be considered in personalised CBC risk models.
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- 2022
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47. Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome
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Zou Pan, Marielle E. van Gijn, Marjolein H. Willemsen, Mariet W. Elting, Susanne Koning, Daniel C. Koboldt, Rebecca Baud, Renzo Guerrini, Ghayda M. Mirzaa, Laurence E. Walsh, Kim L. McBride, Jenny Thies, Andrew E. Timms, Shaoping Huang, Gretchen E. Rosso, Joshua Scheck, Haley McConkey, Matthew A. Deardorff, Peter D. Turnpenny, Suzanne M. Leal, Sanjay M. Sisodiya, Lin Yang, Melissa Lees, Cacha M.P.C.D. Peeters-Scholte, Henry Houlden, Marielle Alders, J. Austin Hamm, Karla A. Peña-Guerra, Richard E. Person, Leena Lauronen, Hannah K. Robinson, Theresa Mihalic Mosher, Alexandra Garza-Flores, Victoria Harrison, Tuomo Määttä, Daniela Q.C.M. Barge-Schaapveld, James R. Lupski, Houda Zghal Elloumi, Francisco J. Guzmán-Vega, Tamison Jewett, Siddharth Banka, Barbara W. van Paassen, J. Lawrence Merritt, Angela Sun, Yana Lara-Taranchenko, Irma Järvelä, Ivan K. Chinn, Claudia A. L. Ruivenkamp, Nicholas M. Allen, Xiaodong Wang, Amy Crunk, Selina H. Banu, Maura R.Z. Ruzhnikov, Jeffery McGlothlin, Mashaya Zaman, Adam Jackson, Stefan T. Arold, Bert B.A. de Vries, Jing Peng, Lauren Schenck, Isabelle Schrauwen, Marjon van Slegtenhorst, Luis Alberto Pedroza, Bekim Sadikovic, Annalisa Vetro, Reshmi Ramakrishnan, Kristin G. Monaghan, Kelly J. Cardona-Londoño, Catherine Quindipan, Kristina Lanko, Rolph Pfundt, Caroline M. Kehoe, Martino Montomoli, Christian Gilissen, Hamid Galehdari, Yolande van Bever, Jennifer Keller-Ramey, Sadegheh Haghshenas, Neda Mazaheri, Stephanie Efthymiou, Reza Maroofian, Lewis Pang, Fleur Vansenne, Abeltje M. Polstra, Kara C. Klemp, Marjolein J.A. Weerts, Xi Lin, Julia Baptista, Tahsin Stefan Barakat, Anneke Kievit, Adi Reich, Stephen R. Braddock, Shehla Mohammed, Abbey M. Putnam, Jennifer Kerkhof, Matthew Pastore, Sally Ann Lynch, Graduate School, ANS - Neuroinfection & -inflammation, Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, MUMC+: DA KG Polikliniek (9), RS: FHML non-thematic output, Human genetics, VU University medical center, Amsterdam Reproduction & Development (AR&D), Clinical Genetics, Irma Järvelä / Principal Investigator, Medicum, Department of Medical and Clinical Genetics, HUS Medical Imaging Center, Clinicum, BioMag Laboratory, HUS Children and Adolescents, and Kliinisen neurofysiologian yksikkö
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Male ,INTELLECTUAL DISABILITY ,GENES ,Language delay ,VARIANTS ,Biology ,Bioinformatics ,3124 Neurology and psychiatry ,Article ,12Q24.31 ,SETD1B ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Neurodevelopmental disorder ,Seizures ,Intellectual disability ,medicine ,Humans ,MICRODELETION ,Global developmental delay ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,3112 Neurosciences ,RECOGNITION ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,Histone-Lysine N-Methyltransferase ,medicine.disease ,Penetrance ,Human genetics ,Phenotype ,Neurodevelopmental Disorders ,MOTIF ,Autism ,METHYLTRANSFERASE ,3111 Biomedicine ,030217 neurology & neurosurgery - Abstract
Contains fulltext : 243955.pdf (Publisher’s version ) (Open Access) PURPOSE: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. METHODS: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. RESULTS: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. CONCLUSION: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.
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- 2021
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48. The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant
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Lakeman, Inge M. M., Van Den Broek, Alexandra J., Vos, Juliën A. M., Barnes, Daniel R., Adlard, Julian, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Balmaña, Judith, Barrowdale, Daniel, Giraud, Sophie, Golmard, Lisa, Hake, Christopher R., Houdayer, Claude, Risch, Harvey A., Lasset, Christine, Laurent, Maïté, Spurdle, Amanda B., Hooning, Maartje J., Hopper, John L., Kets, Carolien M., Leroux, Dominique, Longy, Michel, Mari, Véronique, Mazoyer, Sylvie, Mebirouk, Noura, Mortemousque, Isabelle, Blok, Marinus J., Prieur, Fabienne, Hamann, Ute, Pujol, Pascal, Konstantopoulou, Irene, Heemskerk Gerritsen, Bernadette A. M., Isaacs, Claudine, Saule, Claire, Piedmonte, Marion, Schuster, Helene, Sevenet, Nicolas, Sobol, Hagay, Sokolowska, Johanna, Gómez Garcia, Encarna B., Venat Bouvet, Laurence, Claes, Kathleen B. M., Ahmed, Munaza, Teixeira, Manuel R., Barwell, Julian, Brady, Angela, Izatt, Louise, Hogervorst, Frans B. L., Brennan, Paul, Harrington, Patricia A., Henderson, Alex, Hodgson, Shirley, Kwong, Ava, Borg, Ake, Kennedy, M. John, Porteous, Mary E., Rogers, Mark T., Side, Lucy E., Snape, Katie, Walker, Lisa, Collée, J. Margriet, Jakubowska, Anna, Couch, Fergus J., Hahnen, Eric, Daly, Mary B., Dennis, Joe, Teo, Soo Hwang, Jensen, Uffe Birk, Rantala, Johanna, Dhawan, Mallika, Benitez, Javier, Domchek, Susan M., Eeles, Ros, Engel, Christoph, Legrand, Clémentine, Evans, D. Gareth, James, Paul A., Feliubadaló i Elorza, Maria Lídia, Teulé-Vega, Àlex, Foretova, Lenka, Castera, Laurent, Friedman, Eitan, Frost, Debra, Rennert, Gad, Ganz, Patricia A., Leslie, Goska, Garber, Judy, Hulick, Peter J., Imyanitov, Evgeny N., Glendon, Gord, Thomassen, Mads, Janavicius, Ramunas, Mulligan, Anna Marie, Hollestelle, Antoinette, Jager, Agnes, Koppert, Linetta B., Cook, Jackie, Koudijs, Marco, Kriege, Mieke, Meijers Heijboer, Hanne E. J., Schmutzler, Rita K., Mensenkamp, Arjen R., Dunning, Alison M., Mooij, Thea M., Oosterwijk, Jan C., Caux Moncoutier, Virginie, Singer, Christian F., Berthet, Pascaline, Caldés, Trinidad, Van den Ouweland, Ans M. W., Van der Baan, Frederieke H., Van der Hout, Annemieke H., Van der Kolk, Lizet E., Van der Luijt, Rob B., Thull, Darcy L., Van Deurzen, Carolien H. M., Sharma, Priyanka, Van Doorn, Helena C., Bignon, Yves Jean, Colas, Chrystelle, Van Engelen, Klaartje, Brewer, Carole, Van Hest, Liselotte P., Van Os, Theo A. M., Caligo, Maria A., Verhoef, Senno, Tischkowitz, Marc, Vogel, Maartje J., Wijnen, Juul T., Lalloo, Fiona, Beesley, Jonathan, Fox, Stephen, Collonge Rame, Marie Agnès, Simard, Jacques, Holland, Helene, Jiao, Yue, John, Esther M., Joseph, Vijai, Gerdes, Anne Marie, Karlan, Beth Y., Lesueur, Fabienne, Loud, Jennifer T., Lubiński, Jan, Manoukian, Siranoush, Mcguffog, Lesley, Miller, Austin, Coupier, Isabelle, Gomes, Denise Molina, Barouk Simonet, Emmanuelle, Montagna, Marco, Miller, Clare, Elan, Camille, Davidson, Rosemarie, Mouret Fourme, Emmanuelle, Gayther, Simon A., Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Pauw, Antoine de, Olah, Edith, Morrison, Patrick J., Olopade, Olufunmilayo I., Van Asperen, Christi J., Park, Sue K., Parsons, Michael T., Donaldson, Alan, Belotti, Muriel, Peterlongo, Paolo, Stadler, Zsofia, Stoppa Lyonnet, Dominique, Sutter, Christian, Ong, Kai Ren, Delnatte, Capucine, Tan, Yen Yen, Toland, Amanda E., Tung, Nadine, Van Rensburg, Elizabeth J., Vega, Ana, Wappenschmidt, Barbara, Devilee, Peter, Eason, Jacqueline, Chung, Wendy K., Bernstein, Jonine L., Offit, Kenneth, Aalfs, Cora M., Hanson, Helen, Godwin, Andrew K., Easton, Douglas F., Bonadona, Valérie, Rookus, Matti A., Chenevix-Trench, Georgia, Antoniou, Antonis C., O’shaughnessy Kirwan, Aoife, Robson, Mark, Eccles, Diana M., Schmidt, Marjanka K., Adank, Muriel A., Gemo Study Collaborators, Phillips, Kelly Anne, Embrace Collaborators, Ocgn Investigators, Goldgar, David E., Hebon Investigators, Perkins, Jo, Kconfab Investigators, Bressac de Paillerets, Brigitte, Buecher, Bruno, Caputo, Sandrine, Ausems, Margreet G. E. M., Gregory, Helen, Caron, Olivier, Faivre, Laurence, Fert Ferrer, Sandra, Gauthier Villars, Marion, Radice, Paolo, Gesta, Paul, Clinical Genetics, Medical Oncology, Surgery, Pathology, Gynecological Oncology, Schmidt, Marjanka K. [0000-0002-2228-429X], Apollo - University of Cambridge Repository, Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Schmidt, Marjanka K [0000-0002-2228-429X], HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Institut Català de la Salut, [Lakeman IMM] Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. [van den Broek AJ, Vos JAM] Division of Molecular Pathology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. [Barnes DR] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Adlard J] Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK. [Andrulis IL] Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. [Balmaña J] Hereditary cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Pediatric surgery, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, CCA - Cancer biology and immunology, Epidemiology and Data Science, Human Genetics, ARD - Amsterdam Reproduction and Development, APH - Personalized Medicine, APH - Quality of Care, Chapel Allerton Hospital, University of Leeds, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Reykjavík University, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, The University of Texas M.D. Anderson Cancer Center [Houston], Unitat d'Alt Risc i Prevenció del Càncer, Vall d'Hebron University Hospital [Barcelona], University of Cambridge [UK] (CAM), Group of Human Genetics, Human Cancer Genetics Programme, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Section of Genetic Oncology, University of Pisa - Università di Pisa, Columbia University [New York], Ghent University Hospital, Department of Clinical Genetics, Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Laboratory Medicine and Pathology, Mayo Clinic, Division of Population Science, Fox Chase Cancer Center, Institut Curie [Paris], Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL), CHU Grenoble, CHI Poissy-Saint-Germain, Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), MUMC+: DA KG Polikliniek (9), and Klinische Genetica
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0301 basic medicine ,Percentile ,Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [DISEASES] ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,SUSCEPTIBILITY ALLELES ,Diàtesi ,FAMILIES ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,MESH: BRCA2 Protein ,Breast cancer ,0302 clinical medicine ,MESH: Risk Factors ,Risk Factors ,Other subheadings::/diagnosis [Other subheadings] ,Medicine and Health Sciences ,Medicine ,Mama - Càncer - Diagnòstic ,Family history ,skin and connective tissue diseases ,Genetics (clinical) ,MESH: Heterozygote ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,Factors de risc en les malalties ,BRCA1 Protein ,Hazard ratio ,MESH: Genetic Predisposition to Disease ,1184 Genetics, developmental biology, physiology ,article ,OVARIAN ,BRCA2 Protein/genetics ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,3. Good health ,030220 oncology & carcinogenesis ,Female ,Malalties congènites ,Adult ,Heterozygote ,medicine.medical_specialty ,MESH: Mutation ,Risk factors in diseases ,Otros calificadores::/diagnóstico [Otros calificadores] ,Breast Neoplasms ,Context (language use) ,MUTATION CARRIERS ,Càncer de mama ,afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::susceptibilidad a enfermedades::predisposición genética a la enfermedad [ENFERMEDADES] ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Internal medicine ,Humans ,Genetic Predisposition to Disease ,MESH: BRCA1 Protein ,Retrospective Studies ,BRCA2 Protein ,MESH: Humans ,business.industry ,Proportional hazards model ,CONSORTIUM ,Breast Neoplasms/diagnosis ,MESH: Adult ,MESH: Retrospective Studies ,Retrospective cohort study ,medicine.disease ,Confidence interval ,030104 developmental biology ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Mutation ,BRCA1 Protein/genetics ,3111 Biomedicine ,business ,MESH: Female ,MESH: Breast Neoplasms - Abstract
Predicció de risc de càncer de mama; Dones europees; Variant patògena heterozigota Predicción del riesgo de cáncer de mama; Mujeres europeas; Variante patógena heterocigota Breast cancer risk prediction; European women; Heterozygous pathogenic variant Purpose To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06–1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07–1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC
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- 2021
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49. A second cohort of CHD3 patients expands the molecular mechanisms known to cause Snijders Blok-Campeau syndrome
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Ann Seman, Rixa Woitschach, Duygu Selcen, Divya Nair, Lauren Gunderson, Mahim Jain, Sha Tang, Giuseppe Zampino, Julien L. Marcadier, Marielle Alders, Jason Pinner, Melanie Napier, Linda Hasadsri, Marina Macchiaiolo, Alyssa Blesson, Pavel N. Pichurin, Joseph T. Alaimo, Arjan Bouman, Philippe M. Campeau, Catherine Karimov, Chitra Prasad, Anne Dieux-Coeslier, Nicole L. Bertsch, Bernd Wollnik, Janine Altmüller, Zöe Powis, Holly Dubbs, Tahsin Stefan Barakat, Gregory M. Cooper, Kristen J. Rasmussen, Perrine Brunelle, Patrick R. Blackburn, Erica D. Smith, Jeff M. Milunsky, Katja Kloth, E. Martina Bebin, Lot Snijders Blok, Knut Brockmann, Karin Weiss, Xilma R. Ortiz-Gonzalez, Danna Gal, Dong Li, Francesca Clementina Radio, Joan M. Stoler, Elaine H. Zackai, Jiddeke M. van de Kamp, Deepali N. Shinde, Huifang Yan, Thomas Smol, Alejandro Ferrer, Dagmar Weise, Baiba Lace, Deborah L. Renaud, Lauren E. Bartik, Beth Keena, Michelle L. Thompson, Carol J Saunders, Theodore G. Drivas, Elizabeth J. Bhoj, Eric T. Rush, Marco Tartaglia, Eric W. Klee, Margit Burmeister, Jingmin Wang, Jonas Denecke, Clinical genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Gastroenterology Endocrinology Metabolism, Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, and Clinical Genetics
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Adult ,Male ,CHD3 variants ,Genetic testing ,Adolescent ,Snijders Blok-Campeau syndrome ,Developmental Disabilities ,medicine.disease_cause ,Pediatrics ,Article ,Chromodomain ,Craniofacial Abnormalities ,Catalytic Domain ,Intellectual Disability ,Genetics ,medicine ,Missense mutation ,Humans ,Child ,Genetics (clinical) ,Mutation ,medicine.diagnostic_test ,biology ,Significant difference ,DNA Helicases ,Helicase ,Infant ,Syndrome ,Autism spectrum disorders ,Phenotype ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Child, Preschool ,Cohort ,biology.protein ,Female ,Mi-2 Nucleosome Remodeling and Deacetylase Complex - Abstract
There has been one previous report of a cohort of patients with variants in Chromodomain Helicase DNA-binding 3 (CHD3), now recognized as Snijders Blok-Campeau syndrome. However, with only three previously-reported patients with variants outside the ATPase/helicase domain, it was unclear if variants outside of this domain caused a clinically similar phenotype. We have analyzed 24 new patients with CHD3 variants, including nine outside the ATPase/helicase domain. All patients were detected with unbiased molecular genetic methods. There is not a significant difference in the clinical or facial features of patients with variants in or outside this domain. These additional patients further expand the clinical and molecular data associated with CHD3 variants. Importantly we conclude that there is not a significant difference in the phenotypic features of patients with various molecular disruptions, including whole gene deletions and duplications, and missense variants outside the ATPase/helicase domain. This data will aid both clinical geneticists and molecular geneticists in the diagnosis of this emerging syndrome.
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- 2020
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50. Subclinical myocardial dysfunction is revealed by speckle tracking echocardiography in patients with Cornelia de Lange syndrome
- Author
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Laura Trujillano, Ariadna Ayerza-Casas, Beatriz Puisac, Gonzalo González García, Ángela Ascaso, Ana Latorre-Pellicer, María Arnedo, Cristina Lucia-Campos, Marta Gil-Salvador, Frank J. Kaiser, Feliciano J. Ramos, Juan Pié, Gloria Bueno-Lozano, Institut Català de la Salut, [Trujillano L] Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology-Legal Medicine, School of Medicine, Universidad de Zaragoza, CIBERERGCV02 and IIS-Aragon, Zaragoza, Spain. Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Medicina Genètica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Department of Pediatrics, Hospital Clínico Universitario 'Lozano Blesa', CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain. [Ayerza-Casas A] Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology-Legal Medicine, School of Medicine, Universidad de Zaragoza, CIBERERGCV02 and IIS-Aragon, Zaragoza, Spain. Department of Pediatrics, Hospital Universitario Miguel Servet, Zaragoza, Spain. [Puisac B, Ascaso Á, Latorre-Pellicer A] Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology-Legal Medicine, School of Medicine, Universidad de Zaragoza, CIBERERGCV02 and IIS-Aragon, Zaragoza, Spain. [González García G] Department of Pediatrics, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Heart Defects, Congenital ,diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::técnicas de imagen cardíaca::ecocardiografía [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Adolescent ,Miocardi - Malalties - Diagnòstic ,Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Cardiac Imaging Techniques::Echocardiography [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Otros calificadores::/diagnóstico [Otros calificadores] ,Medizin ,Stroke Volume ,Cell Cycle Proteins ,enfermedades del sistema nervioso::manifestaciones neurológicas::manifestaciones neuroconductuales::discapacidad intelectual::síndrome de De Lange [ENFERMEDADES] ,Histone Deacetylases ,Repressor Proteins ,Cardiovascular Diseases::Heart Diseases::Cardiomyopathies [DISEASES] ,Predictive Value of Tests ,Echocardiography ,De Lange Syndrome ,enfermedades cardiovasculares::enfermedades cardíacas::miocardiopatías [ENFERMEDADES] ,Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability::De Lange Syndrome [DISEASES] ,Other subheadings::/diagnosis [Other subheadings] ,Humans ,Discapacitat intel·lectual ,Child ,Cardiomyopathies ,Ecocardiografia - Abstract
Echocardiography; Lange syndrome; Myocardial dysfunction Ecocardiografia; Síndrome de Lange; Disfunció miocàrdica Ecocardiografía; Síndrome de Lange; Disfunción miocárdica This study assesses a possible cardiac dysfunction in individuals with Cornelia de Lange syndrome (CdLS) without diagnosed congenital heart disease (CHD) and its association with other factors. Twenty patients and 20 controls were included in the study divided into three age-dependent groups (A: 20 yrs), and were evaluated using conventional echocardiography, tissue doppler imaging (TDI), two-dimensional speckle tracking and genetic and biochemical analyses. The left ventricular global longitudinal strain (GLS) was altered (
- Published
- 2022
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