127 results on '"Azzarello-Burri, Silvia"'
Search Results
2. De Novo Pathogenic Variants in N-cadherin Cause a Syndromic Neurodevelopmental Disorder with Corpus Collosum, Axon, Cardiac, Ocular, and Genital Defects
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Accogli, Andrea, Calabretta, Sara, St-Onge, Judith, Boudrahem-Addour, Nassima, Dionne-Laporte, Alexandre, Joset, Pascal, Azzarello-Burri, Silvia, Rauch, Anita, Krier, Joel, Fieg, Elizabeth, Pallais, Juan C, Network, Undiagnosed Diseases, Acosta, Maria T, Adams, David R, Agrawal, Pankaj, Alejandro, Mercedes E, Allard, Patrick, Alvey, Justin, Andrews, Ashley, Ashley, Euan A, Azamian, Mahshid S, Bacino, Carlos A, Bademci, Guney, Baker, Eva, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Barbouth, Deborah, Batzli, Gabriel F, Bayrak-Toydemir, Pinar, Beggs, Alan H, Bejerano, Gill, Bellen, Hugo J, Bernstein, Jonathan A, Berry, Gerard T, Bican, Anna, Bick, David P, Birch, Camille L, Bivona, Stephanie, Bohnsack, John, Bonnenmann, Carsten, Bonner, Devon, Boone, Braden E, Bostwick, Bret L, Botto, Lorenzo, Briere, Lauren C, Brokamp, Elly, Brown, Donna M, Brush, Matthew, Burke, Elizabeth A, Burrage, Lindsay C, Butte, Manish J, Carey, John, Carrasquillo, Olveen, Chang, Ta Chen Peter, Chao, Hsiao-Tuan, Clark, Gary D, Coakley, Terra R, Cobban, Laurel A, Cogan, Joy D, Cole, F Sessions, Colley, Heather A, Cooper, Cynthia M, Cope, Heidi, Craigen, William J, D’Souza, Precilla, Dasari, Surendra, Davids, Mariska, Dayal, Jyoti G, Dell’Angelica, Esteban C, Dhar, Shweta U, Dorrani, Naghmeh, Dorset, Daniel C, Douine, Emilie D, Draper, David D, Duncan, Laura, Eckstein, David J, Emrick, Lisa T, Eng, Christine M, Esteves, Cecilia, Estwick, Tyra, Fernandez, Liliana, Ferreira, Carlos, Fieg, Elizabeth L, Fisher, Paul G, Fogel, Brent L, Forghani, Irman, Fresard, Laure, Gahl, William A, Godfrey, Rena A, Goldman, Alica M, Goldstein, David B, Gourdine, Jean-Philippe F, Grajewski, Alana, Groden, Catherine A, Gropman, Andrea L, Haendel, Melissa, Hamid, Rizwan, Hanchard, Neil A, and Hayes, Nichole
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Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Genetics ,Biological Sciences ,Neurosciences ,2.1 Biological and endogenous factors ,Aetiology ,Axons ,Cadherins ,Corpus Callosum ,Eye ,Frameshift Mutation ,Genitalia ,Heart Defects ,Congenital ,Heterozygote ,Humans ,Neurodevelopmental Disorders ,Undiagnosed Diseases Network ,ACOG ,CDH2 ,N-cadherin ,cardiac defects ,cell-cell adhesion ,corpus callosum ,eye defects ,genital defects ,intellectual disability ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Cadherins constitute a family of transmembrane proteins that mediate calcium-dependent cell-cell adhesion. The extracellular domain of cadherins consists of extracellular cadherin (EC) domains, separated by calcium binding sites. The EC interacts with other cadherin molecules in cis and in trans to mechanically hold apposing cell surfaces together. CDH2 encodes N-cadherin, whose essential roles in neural development include neuronal migration and axon pathfinding. However, CDH2 has not yet been linked to a Mendelian neurodevelopmental disorder. Here, we report de novo heterozygous pathogenic variants (seven missense, two frameshift) in CDH2 in nine individuals with a syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, variable axon pathfinding defects (corpus callosum agenesis or hypoplasia, mirror movements, Duane anomaly), and ocular, cardiac, and genital anomalies. All seven missense variants (c.1057G>A [p.Asp353Asn]; c.1789G>A [p.Asp597Asn]; c.1789G>T [p.Asp597Tyr]; c.1802A>C [p.Asn601Thr]; c.1839C>G [p.Cys613Trp]; c.1880A>G [p.Asp627Gly]; c.2027A>G [p.Tyr676Cys]) result in substitution of highly conserved residues, and six of seven cluster within EC domains 4 and 5. Four of the substitutions affect the calcium-binding site in the EC4-EC5 interdomain. We show that cells expressing these variants in the EC4-EC5 domains have a defect in cell-cell adhesion; this defect includes impaired binding in trans with N-cadherin-WT expressed on apposing cells. The two frameshift variants (c.2563_2564delCT [p.Leu855Valfs∗4]; c.2564_2567dupTGTT [p.Leu856Phefs∗5]) are predicted to lead to a truncated cytoplasmic domain. Our study demonstrates that de novo heterozygous variants in CDH2 impair the adhesive activity of N-cadherin, resulting in a multisystemic developmental disorder, that could be named ACOG syndrome (agenesis of corpus callosum, axon pathfinding, cardiac, ocular, and genital defects).
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- 2019
3. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy
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O’Donnell-Luria, Anne H, Pais, Lynn S, Faundes, Víctor, Wood, Jordan C, Sveden, Abigail, Luria, Victor, Jamra, Rami Abou, Accogli, Andrea, Amburgey, Kimberly, Anderlid, Britt Marie, Azzarello-Burri, Silvia, Basinger, Alice A, Bianchini, Claudia, Bird, Lynne M, Buchert, Rebecca, Carre, Wilfrid, Ceulemans, Sophia, Charles, Perrine, Cox, Helen, Culliton, Lisa, Currò, Aurora, Study, Deciphering Developmental Disorders, McRae, Jeremy F, Clayton, Stephen, Fitzgerald, Tomas W, Kaplanis, Joanna, Prigmore, Elena, Rajan, Diana, Sifrim, Alejandro, Aitken, Stuart, Akawi, Nadia, Alvi, Mohsan, Ambridge, Kirsty, Barrett, Daniel M, Bayzetinova, Tanya, Jones, Philip, Jones, Wendy D, King, Daniel, Krishnappa, Netravathi, Mason, Laura E, Singh, Tarjinder, Tivey, Adrian R, Ahmed, Munaza, Anjum, Uruj, Archer, Hayley, Armstrong, Ruth, Awada, Jana, Balasubramanian, Meena, Banka, Siddharth, Baralle, Diana, Barnicoat, Angela, Batstone, Paul, Baty, David, Bennett, Chris, Berg, Jonathan, Bernhard, Birgitta, Bevan, A Paul, Bitner-Glindzicz, Maria, Blair, Edward, Blyth, Moira, Bohanna, David, Bourdon, Louise, Bourn, David, Bradley, Lisa, Brady, Angela, Brent, Simon, Brewer, Carole, Brunstrom, Kate, Bunyan, David J, Burn, John, Canham, Natalie, Castle, Bruce, Chandler, Kate, Chatzimichali, Elena, Cilliers, Deirdre, Clarke, Angus, Clasper, Susan, Clayton-Smith, Jill, Clowes, Virginia, Coates, Andrea, Cole, Trevor, Colgiu, Irina, Collins, Amanda, Collinson, Morag N, Connell, Fiona, Cooper, Nicola, Cresswell, Lara, Cross, Gareth, Crow, Yanick, D’Alessandro, Mariella, Dabir, Tabib, Davidson, Rosemarie, Davies, Sally, de Vries, Dylan, Dean, John, Deshpande, Charu, Devlin, Gemma, Dixit, Abhijit, and Dobbie, Angus
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Biological Sciences ,Genetics ,Autism ,Neurosciences ,Brain Disorders ,Neurodegenerative ,Intellectual and Developmental Disabilities (IDD) ,Pediatric ,Clinical Research ,Epilepsy ,Mental Health ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Adolescent ,Adult ,Child ,Child ,Preschool ,DNA-Binding Proteins ,Female ,Genetic Variation ,Haploinsufficiency ,Heterozygote ,Humans ,Infant ,Male ,Neurodevelopmental Disorders ,Pedigree ,Phenotype ,Young Adult ,Deciphering Developmental Disorders (DDD) Study ,H3K4 methylation ,KMT2E ,autism ,epilepsy ,epileptic encephalopathy ,global developmental delay ,intellectual disability ,neurodevelopmental disorder ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.
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- 2019
4. Genome-wide non-invasive prenatal testing in single- and multiple-pregnancies at any risk: Identification of maternal polymorphisms to reduce the number of unnecessary invasive confirmation testing
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Oneda, Beatrice, Sirleto, Pietro, Baldinger, Rosa, Taralczak, Malgorzata, Joset, Pascal, Zweier, Markus, Niedrist, Dunja, Azzarello-Burri, Silvia, Britschgi, Christian, Breymann, Christian, Ochsenbein-Kölble, Nicole, Burkhardt, Tilo, Wisser, Josef, Zimmermann, Roland, Steindl, Katharina, and Rauch, Anita
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- 2020
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5. Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly
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Boonsawat, Paranchai, Joset, Pascal, Steindl, Katharina, Oneda, Beatrice, Gogoll, Laura, Azzarello-Burri, Silvia, Sheth, Frenny, Datar, Chaitanya, Verma, Ishwar C., Puri, Ratna Dua, Zollino, Marcella, Bachmann-Gagescu, Ruxandra, Niedrist, Dunja, Papik, Michael, Figueiro-Silva, Joana, Masood, Rahim, Zweier, Markus, Kraemer, Dennis, Lincoln, Sharyn, Rodan, Lance, Passemard, Sandrine, Drunat, Séverine, Verloes, Alain, Horn, Anselm H.C., Sticht, Heinrich, Steinfeld, Robert, Plecko, Barbara, Latal, Beatrice, Jenni, Oskar, Asadollahi, Reza, and Rauch, Anita
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- 2019
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6. The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study
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Papuc, Sorina M., Abela, Lucia, Steindl, Katharina, Begemann, Anaïs, Simmons, Thomas L., Schmitt, Bernhard, Zweier, Markus, Oneda, Beatrice, Socher, Eileen, Crowther, Lisa M., Wohlrab, Gabriele, Gogoll, Laura, Poms, Martin, Seiler, Michelle, Papik, Michael, Baldinger, Rosa, Baumer, Alessandra, Asadollahi, Reza, Kroell-Seger, Judith, Schmid, Regula, Iff, Tobias, Schmitt-Mechelke, Thomas, Otten, Karoline, Hackenberg, Annette, Addor, Marie-Claude, Klein, Andrea, Azzarello-Burri, Silvia, Sticht, Heinrich, Joset, Pascal, Plecko, Barbara, and Rauch, Anita
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- 2019
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7. Clinical and experimental evidence suggest a link between KIF7 and C5orf42-related ciliopathies through Sonic Hedgehog signaling
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Asadollahi, Reza, Strauss, Justin E, Zenker, Martin, Beuing, Oliver, Edvardson, Simon, Elpeleg, Orly, Strom, Tim M, Joset, Pascal, Niedrist, Dunja, Otte, Christine, Oneda, Beatrice, Boonsawat, Paranchai, Azzarello-Burri, Silvia, Bartholdi, Deborah, Papik, Michael, Zweier, Markus, Haas, Cordula, Ekici, Arif B, Baumer, Alessandra, Boltshauser, Eugen, Steindl, Katharina, Nothnagel, Michael, Schinzel, Albert, Stoeckli, Esther T, and Rauch, Anita
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- 2018
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8. Maladie de von Hippel-Lindau
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Koster, Kira-Lee, primary, Rothermundt, Christian, additional, Binet, Isabelle, additional, Borovicka, Jan, additional, Bozinov, Oliver, additional, Clerici, Thomas, additional, Engeler, Daniel S., additional, Greiner, Jeanette, additional, Hader, Claudia, additional, Heinimann, Karl, additional, Azzarello-Burri, Silvia, additional, Lang, Corina, additional, Krull, Ina, additional, Stckli, Sandro J., additional, Omlin, Aurelius, additional, and Hundsberger, Thomas, additional
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- 2022
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9. Von-Hippel-Lindau-Erkrankung
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Koster, Kira-Lee, primary, Rothermundt, Christian, additional, Binet, Isabelle, additional, Borovicka, Jan, additional, Bozinov, Oliver, additional, Clerici, Thomas, additional, Engeler, Daniel S., additional, Greiner, Jeanette, additional, Hader, Claudia, additional, Heinimann, Karl, additional, Azzarello-Burri, Silvia, additional, Lang, Corina, additional, Krull, Ina, additional, Stckli, Sandro J., additional, Omlin, Aurelius, additional, and Hundsberger, Thomas, additional
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- 2022
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10. Horizontal Gaze Palsy in Two Brothers with Compound Heterozygous ROBO3 Gene Mutations
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Hackenberg, Annette, Boltshauser, Eugen, Gerth-Kahlert, Christina, Stahr, Nikolai, Azzarello-Burri, Silvia, and Plecko, Barbara
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- 2017
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11. Molekulargenetik und Molekularpathologie beim Prostatakarzinom
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Omlin, Aurelius, Pratsinis, Manolis, Stoll, Susanna, Riniker, Salome, Hess Soom, Julie, Förbs, Diana, Padberg Sgier, Barbara, Azzarello-Burri, Silvia; https://orcid.org/0000-0001-8911-3500, Rothermundt, Christian; https://orcid.org/0000-0002-2104-7794, Omlin, Aurelius, Pratsinis, Manolis, Stoll, Susanna, Riniker, Salome, Hess Soom, Julie, Förbs, Diana, Padberg Sgier, Barbara, Azzarello-Burri, Silvia; https://orcid.org/0000-0001-8911-3500, and Rothermundt, Christian; https://orcid.org/0000-0002-2104-7794
- Abstract
Beim häufigsten bösartigen Tumor des Mannes, dem Prostatakarzinom, konnten in den letzten Jahren grosse Fortschritte im Bereich der molekularpathologischen Charakterisierung erzielt werden. Diese Erkenntnisse haben entscheidend zur Entwicklung zielgerichteter Therapien in fortgeschrittenen Stadien des Prostatakarzinoms beigetragen. Die molekularpathologischen Ergebnisse geben zudem wichtige Hinweise auf eine mögliche genetische Prädisposition.
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- 2022
12. La génétique et la pathologie moléculaires dans le cancer de la prostate
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Omlin, Aurelius, primary, Pratsinis, Manolis, additional, Stoll, Susanna, additional, Riniker, Salom, additional, Hess Soom, Julie, additional, Frbs, Diana, additional, Padberg Sgier, Barbara, additional, Azzarello-Burri, Silvia, additional, and Rothermundt, Christian, additional
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- 2022
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13. Molekulargenetik und Molekularpathologie beim Prostatakarzinom
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Omlin, Aurelius, primary, Pratsinis, Manolis, additional, Stoll, Susanna, additional, Riniker, Salom, additional, Hess Soom, Julie, additional, Frbs, Diana, additional, Padberg Sgier, Barbara, additional, Azzarello-Burri, Silvia, additional, and Rothermundt, Christian, additional
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- 2022
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14. Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans
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Collier, Jack J, Guissart, Claire, Oláhová, Monika, Sasorith, Souphatta, Piron-Prunier, Florence, et al, Bahr, Angela, Azzarello-Burri, Silvia, Rauch, Anita, and University of Zurich
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10039 Institute of Medical Genetics ,570 Life sciences ,biology ,610 Medicine & health ,2700 General Medicine - Published
- 2021
15. Update Swiss guideline for counselling and testing for predisposition to breast, ovarian, pancreatic and prostate cancer
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Stoll, Susanna, primary, Unger, Sheila, additional, Azzarello-Burri, Silvia, additional, Chappuis, Pierre, additional, Graffeo, Rossella, additional, Pichert, Gabriella, additional, Röthlisberger, Benno, additional, Taban, Francois, additional, and Riniker, Salome, additional
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- 2021
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16. Boy with autosomal recessive polycystic kidney and autosomal dominant polycystic liver disease
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Zingg-Schenk, Andrea, Caduff, Jürg, Azzarello-Burri, Silvia, Bergmann, Carsten, Drenth, Joost P. H., and Neuhaus, Thomas J.
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- 2012
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17. The clinical significance of small copy number variants in neurodevelopmental disorders
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Asadollahi, Reza, Oneda, Beatrice, Joset, Pascal, Azzarello-Burri, Silvia, Bartholdi, Deborah, Steindl, Katharina, Vincent, Marie, Cobilanschi, Joana, Sticht, Heinrich, Baldinger, Rosa, Reissmann, Regina, Sudholt, Irene, Thiel, Christian T, Ekici, Arif B, Reis, André, Bijlsma, Emilia K, Andrieux, Joris, Dieux, Anne, FitzPatrick, David, Ritter, Susanne, Baumer, Alessandra, Latal, Beatrice, Plecko, Barbara, Jenni, Oskar G, and Rauch, Anita
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- 2014
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18. A newly recognized 13q12.3 microdeletion syndrome characterized by intellectual disability, microcephaly, and eczema/atopic dermatitis encompassing the HMGB1 and KATNAL1 genes
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Bartholdi, Deborah, Stray-Pedersen, Asbjrg, Azzarello-Burri, Silvia, Kibaek, Maria, Kirchhoff, Maria, Oneda, Beatrice, Rdningen, Olaug, Schmitt-Mechelke, Thomas, Rauch, Anita, and Kjaergaard, Susanne
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- 2014
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19. Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans
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Collier, Jack J., primary, Guissart, Claire, additional, Oláhová, Monika, additional, Sasorith, Souphatta, additional, Piron-Prunier, Florence, additional, Suomi, Fumi, additional, Zhang, David, additional, Martinez-Lopez, Nuria, additional, Leboucq, Nicolas, additional, Bahr, Angela, additional, Azzarello-Burri, Silvia, additional, Reich, Selina, additional, Schöls, Ludger, additional, Polvikoski, Tuomo M., additional, Meyer, Pierre, additional, Larrieu, Lise, additional, Schaefer, Andrew M., additional, Alsaif, Hessa S., additional, Alyamani, Suad, additional, Zuchner, Stephan, additional, Barbosa, Inês A., additional, Deshpande, Charu, additional, Pyle, Angela, additional, Rauch, Anita, additional, Synofzik, Matthis, additional, Alkuraya, Fowzan S., additional, Rivier, François, additional, Ryten, Mina, additional, McFarland, Robert, additional, Delahodde, Agnès, additional, McWilliams, Thomas G., additional, Koenig, Michel, additional, and Taylor, Robert W., additional
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- 2021
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20. Update Swiss guideline for counselling and testing for predisposition to breast, ovarian, pancreatic and prostate cancer
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Stoll, Susanna, Unger, Sheila, Azzarello-Burri, Silvia; https://orcid.org/0000-0001-8911-3500, Chappuis, Pierre, Graffeo, Rossella, Pichert, Gabriella, Röthlisberger, Benno, Taban, Francois, Riniker, Salome, Stoll, Susanna, Unger, Sheila, Azzarello-Burri, Silvia; https://orcid.org/0000-0001-8911-3500, Chappuis, Pierre, Graffeo, Rossella, Pichert, Gabriella, Röthlisberger, Benno, Taban, Francois, and Riniker, Salome
- Abstract
This paper presents the Swiss guideline for genetic counselling and testing of individuals with an increased probability for carrying mutations in high risk cancer predisposition genes, particularly BRCA1 and BRCA2. It aims to help providers of genetic counselling to identify valuable candidates for testing and serves as a basis for reimbursement claims to Swiss insurance companies.
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- 2021
21. De Novo Pathogenic Variants in N-cadherin Cause a Syndromic Neurodevelopmental Disorder with Corpus Callosum, Axon, Cardiac, Ocular, and Genital Defects
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Acosta, Maria T., Adams, David R., Agrawal, Pankaj, Alejandro, Mercedes E., Allard, Patrick, Alvey, Justin, Andrews, Ashley, Ashley, Euan A., Azamian, Mahshid S., Bacino, Carlos A., Bademci, Guney, Baker, Eva, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Barbouth, Deborah, Batzli, Gabriel F., Bayrak-Toydemir, Pinar, Beggs, Alan H., Bejerano, Gill, Bellen, Hugo J., Bernstein, Jonathan A., Berry, Gerard T., Bican, Anna, Bick, David P., Birch, Camille L., Bivona, Stephanie, Bohnsack, John, Bonnenmann, Carsten, Bonner, Devon, Boone, Braden E., Bostwick, Bret L., Botto, Lorenzo, Briere, Lauren C., Brokamp, Elly, Brown, Donna M., Brush, Matthew, Burke, Elizabeth A., Burrage, Lindsay C., Butte, Manish J., Carey, John, Carrasquillo, Olveen, Chang, Ta Chen Peter, Chao, Hsiao-Tuan, Clark, Gary D., Coakley, Terra R., Cobban, Laurel A., Cogan, Joy D., Cole, F. Sessions, Colley, Heather A., Cooper, Cynthia M., Cope, Heidi, Craigen, William J., D’Souza, Precilla, Dasari, Surendra, Davids, Mariska, Dayal, Jyoti G., Dell’Angelica, Esteban C., Dhar, Shweta U., Dorrani, Naghmeh, Dorset, Daniel C., Douine, Emilie D., Draper, David D., Duncan, Laura, Eckstein, David J., Emrick, Lisa T., Eng, Christine M., Esteves, Cecilia, Estwick, Tyra, Fernandez, Liliana, Ferreira, Carlos, Fieg, Elizabeth L., Fisher, Paul G., Fogel, Brent L., Forghani, Irman, Fresard, Laure, Gahl, William A., Godfrey, Rena A., Goldman, Alica M., Goldstein, David B., Gourdine, Jean-Philippe F., Grajewski, Alana, Groden, Catherine A., Gropman, Andrea L., Haendel, Melissa, Hamid, Rizwan, Hanchard, Neil A., Hayes, Nichole, High, Frances, Holm, Ingrid A., Hom, Jason, Huang, Alden, Huang, Yong, Isasi, Rosario, Jamal, Fariha, Jiang, Yong-hui, Johnston, Jean M., Jones, Angela L., Karaviti, Lefkothea, Kelley, Emily G., Kiley, Dana, Koeller, David M., Kohane, Isaac S., Kohler, Jennefer N., Krakow, Deborah, Krasnewich, Donna M., Korrick, Susan, Koziura, Mary, Krier, Joel B., Kyle, Jennifer E., Lalani, Seema R., Lam, Byron, Lanpher, Brendan C., Lanza, Ian R., Lau, C. Christopher, Lazar, Jozef, LeBlanc, Kimberly, Lee, Brendan H., Lee, Hane, Levitt, Roy, Levy, Shawn E., Lewis, Richard A., Lincoln, Sharyn A., Liu, Pengfei, Liu, Xue Zhong, Longo, Nicola, Loo, Sandra K., Loscalzo, Joseph, Maas, Richard L., Macnamara, Ellen F., MacRae, Calum A., Maduro, Valerie V., Majcherska, Marta M., Malicdan, May Christine V., Mamounas, Laura A., Manolio, Teri A., Mao, Rong, Markello, Thomas C., Marom, Ronit, Marth, Gabor, Martin, Beth A., Martin, Martin G., Martínez-Agosto, Julian A., Marwaha, Shruti, May, Thomas, McCauley, Jacob, McConkie-Rosell, Allyn, McCormack, Colleen E., McCray, Alexa T., Metz, Thomas O., Might, Matthew, Morava-Kozicz, Eva, Moretti, Paolo M., Morimoto, Marie, Mulvihill, John J., Murdock, David R., Nath, Avi, Nelson, Stan F., Newberry, J. Scott, Newman, John H., Nicholas, Sarah K., Novacic, Donna, Oglesbee, Devin, Orengo, James P., Pace, Laura, Pak, Stephen, Pallais, J. Carl, Palmer, Christina G.S., Papp, Jeanette C., Parker, Neil H., Phillips, John A., III, Posey, Jennifer E., Postlethwait, John H., Potocki, Lorraine, Pusey, Barbara N., Quinlan, Aaron, Raja, Archana N., Renteria, Genecee, Reuter, Chloe M., Rives, Lynette, Robertson, Amy K., Rodan, Lance H., Rosenfeld, Jill A., Rowley, Robb K., Ruzhnikov, Maura, Sacco, Ralph, Sampson, Jacinda B., Samson, Susan L., Saporta, Mario, Schaechter, Judy, Schedl, Timothy, Schoch, Kelly, Scott, Daryl A., Shakachite, Lisa, Sharma, Prashant, Shashi, Vandana, Shields, Kathleen, Shin, Jimann, Signer, Rebecca, Sillari, Catherine H., Silverman, Edwin K., Sinsheimer, Janet S., Sisco, Kathy, Smith, Kevin S., Solnica-Krezel, Lilianna, Spillmann, Rebecca C., Stoler, Joan M., Stong, Nicholas, Sullivan, Jennifer A., Sutton, Shirley, Sweetser, David A., Tabor, Holly K., Tamburro, Cecelia P., Tan, Queenie K.-G., Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Tifft, Cynthia J., Toro, Camilo, Tran, Alyssa A., Urv, Tiina K., Velinder, Matt, Viskochil, Dave, Vogel, Tiphanie P., Wahl, Colleen E., Walley, Nicole M., Walsh, Chris A., Walker, Melissa, Wambach, Jennifer, Wan, Jijun, Wang, Lee-kai, Wangler, Michael F., Ward, Patricia A., Waters, Katrina M., Webb-Robertson, Bobbie-Jo M., Wegner, Daniel, Westerfield, Monte, Wheeler, Matthew T., Wise, Anastasia L., Wolfe, Lynne A., Woods, Jeremy D., Worthey, Elizabeth A., Yamamoto, Shinya, Yang, John, Yoon, Amanda J., Yu, Guoyun, Zastrow, Diane B., Zhao, Chunli, Zuchner, Stephan, Accogli, Andrea, Calabretta, Sara, St-Onge, Judith, Boudrahem-Addour, Nassima, Dionne-Laporte, Alexandre, Joset, Pascal, Azzarello-Burri, Silvia, Rauch, Anita, Krier, Joel, Fieg, Elizabeth, Pallais, Juan C., McDonald, Marie, Freedman, Sharon F., Rivière, Jean-Baptiste, Lafond-Lapalme, Joël, Simpson, Brittany N., Hopkin, Robert J., Trimouille, Aurélien, Van-Gils, Julien, Begtrup, Amber, McWalter, Kirsty, Delphine, Heron, Keren, Boris, Genevieve, David, Argilli, Emanuela, Sherr, Elliott H., Severino, Mariasavina, Rouleau, Guy A., Yam, Patricia T., Charron, Frédéric, and Srour, Myriam
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- 2019
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22. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy
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McRae, Jeremy F., Clayton, Stephen, Fitzgerald, Tomas W., Kaplanis, Joanna, Prigmore, Elena, Rajan, Diana, Sifrim, Alejandro, Aitken, Stuart, Akawi, Nadia, Alvi, Mohsan, Ambridge, Kirsty, Barrett, Daniel M., Bayzetinova, Tanya, Jones, Philip, Jones, Wendy D., King, Daniel, Krishnappa, Netravathi, Mason, Laura E., Singh, Tarjinder, Tivey, Adrian R., Ahmed, Munaza, Anjum, Uruj, Archer, Hayley, Armstrong, Ruth, Awada, Jana, Balasubramanian, Meena, Banka, Siddharth, Baralle, Diana, Barnicoat, Angela, Batstone, Paul, Baty, David, Bennett, Chris, Berg, Jonathan, Bernhard, Birgitta, Bevan, A. Paul, Bitner-Glindzicz, Maria, Blair, Edward, Blyth, Moira, Bohanna, David, Bourdon, Louise, Bourn, David, Bradley, Lisa, Brady, Angela, Brent, Simon, Brewer, Carole, Brunstrom, Kate, Bunyan, David J., Burn, John, Canham, Natalie, Castle, Bruce, Chandler, Kate, Chatzimichali, Elena, Cilliers, Deirdre, Clarke, Angus, Clasper, Susan, Clayton-Smith, Jill, Clowes, Virginia, Coates, Andrea, Cole, Trevor, Colgiu, Irina, Collins, Amanda, Collinson, Morag N., Connell, Fiona, Cooper, Nicola, Cox, Helen, Cresswell, Lara, Cross, Gareth, Crow, Yanick, D’Alessandro, Mariella, Dabir, Tabib, Davidson, Rosemarie, Davies, Sally, de Vries, Dylan, Dean, John, Deshpande, Charu, Devlin, Gemma, Dixit, Abhijit, Dobbie, Angus, Donaldson, Alan, Donnai, Dian, Donnelly, Deirdre, Donnelly, Carina, Douglas, Angela, Douzgou, Sofia, Duncan, Alexis, Eason, Jacqueline, Ellard, Sian, Ellis, Ian, Elmslie, Frances, Evans, Karenza, Everest, Sarah, Fendick, Tina, Fisher, Richard, Flinter, Frances, Foulds, Nicola, Fry, Andrew, Fryer, Alan, Gardiner, Carol, Gaunt, Lorraine, Ghali, Neeti, Gibbons, Richard, Gill, Harinder, Goodship, Judith, Goudie, David, Gray, Emma, Green, Andrew, Greene, Philip, Greenhalgh, Lynn, Gribble, Susan, Harrison, Rachel, Harrison, Lucy, Harrison, Victoria, Hawkins, Rose, He, Liu, Hellens, Stephen, Henderson, Alex, Hewitt, Sarah, Hildyard, Lucy, Hobson, Emma, Holden, Simon, Holder, Muriel, Holder, Susan, Hollingsworth, Georgina, Homfray, Tessa, Humphreys, Mervyn, Hurst, Jane, Hutton, Ben, Ingram, Stuart, Irving, Melita, Islam, Lily, Jackson, Andrew, Jarvis, Joanna, Jenkins, Lucy, Johnson, Diana, Jones, Elizabeth, Josifova, Dragana, Joss, Shelagh, Kaemba, Beckie, Kazembe, Sandra, Kelsell, Rosemary, Kerr, Bronwyn, Kingston, Helen, Kini, Usha, Kinning, Esther, Kirby, Gail, Kirk, Claire, Kivuva, Emma, Kraus, Alison, Kumar, Dhavendra, Kumar, V. K. Ajith, Lachlan, Katherine, Lam, Wayne, Lampe, Anne, Langman, Caroline, Lees, Melissa, Lim, Derek, Longman, Cheryl, Lowther, Gordon, Lynch, Sally A., Magee, Alex, Maher, Eddy, Male, Alison, Mansour, Sahar, Marks, Karen, Martin, Katherine, Maye, Una, McCann, Emma, McConnell, Vivienne, McEntagart, Meriel, McGowan, Ruth, McKay, Kirsten, McKee, Shane, McMullan, Dominic J., McNerlan, Susan, McWilliam, Catherine, Mehta, Sarju, Metcalfe, Kay, Middleton, Anna, Miedzybrodzka, Zosia, Miles, Emma, Mohammed, Shehla, Montgomery, Tara, Moore, David, Morgan, Sian, Morton, Jenny, Mugalaasi, Hood, Murday, Victoria, Murphy, Helen, Naik, Swati, Nemeth, Andrea, Nevitt, Louise, Newbury-Ecob, Ruth, Norman, Andrew, O’Shea, Rosie, Ogilvie, Caroline, Ong, Kai-Ren, Park, Soo-Mi, Parker, Michael J., Patel, Chirag, Paterson, Joan, Payne, Stewart, Perrett, Daniel, Phipps, Julie, Pilz, Daniela T., Pollard, Martin, Pottinger, Caroline, Poulton, Joanna, Pratt, Norman, Prescott, Katrina, Price, Sue, Pridham, Abigail, Procter, Annie, Purnell, Hellen, Quarrell, Oliver, Ragge, Nicola, Rahbari, Raheleh, Randall, Josh, Rankin, Julia, Raymond, Lucy, Rice, Debbie, Robert, Leema, Roberts, Eileen, Roberts, Jonathan, Roberts, Paul, Roberts, Gillian, Ross, Alison, Rosser, Elisabeth, Saggar, Anand, Samant, Shalaka, Sampson, Julian, Sandford, Richard, Sarkar, Ajoy, Schweiger, Susann, Scott, Richard, Scurr, Ingrid, Selby, Ann, Seller, Anneke, Sequeira, Cheryl, Shannon, Nora, Sharif, Saba, Shaw-Smith, Charles, Shearing, Emma, Shears, Debbie, Sheridan, Eamonn, Simonic, Ingrid, Singzon, Roldan, Skitt, Zara, Smith, Audrey, Smith, Kath, Smithson, Sarah, Sneddon, Linda, Splitt, Miranda, Squires, Miranda, Stewart, Fiona, Stewart, Helen, Straub, Volker, Suri, Mohnish, Sutton, Vivienne, Swaminathan, Ganesh Jawahar, Sweeney, Elizabeth, Tatton-Brown, Kate, Taylor, Cat, Taylor, Rohan, Tein, Mark, Temple, I. Karen, Thomson, Jenny, Tischkowitz, Marc, Tomkins, Susan, Torokwa, Audrey, Treacy, Becky, Turner, Claire, Turnpenny, Peter, Tysoe, Carolyn, Vandersteen, Anthony, Varghese, Vinod, Vasudevan, Pradeep, Vijayarangakannan, Parthiban, Vogt, Julie, Wakeling, Emma, Wallwark, Sarah, Waters, Jonathon, Weber, Astrid, Wellesley, Diana, Whiteford, Margo, Widaa, Sara, Wilcox, Sarah, Wilkinson, Emily, Williams, Denise, Williams, Nicola, Wilson, Louise, Woods, Geoff, Wragg, Christopher, Wright, Michael, Yates, Laura, Yau, Michael, Nellåker, Chris, Parker, Michael, Firth, Helen V., Wright, Caroline F., FitzPatrick, David R., Barrett, Jeffrey C., Hurles, Matthew E., O’Donnell-Luria, Anne H., Pais, Lynn S., Faundes, Víctor, Wood, Jordan C., Sveden, Abigail, Luria, Victor, Abou Jamra, Rami, Accogli, Andrea, Amburgey, Kimberly, Anderlid, Britt Marie, Azzarello-Burri, Silvia, Basinger, Alice A., Bianchini, Claudia, Bird, Lynne M., Buchert, Rebecca, Carre, Wilfrid, Ceulemans, Sophia, Charles, Perrine, Culliton, Lisa, Currò, Aurora, Demurger, Florence, Dowling, James J., Duban-Bedu, Benedicte, Dubourg, Christèle, Eiset, Saga Elise, Escobar, Luis F., Ferrarini, Alessandra, Haack, Tobias B., Hashim, Mona, Heide, Solveig, Helbig, Katherine L., Helbig, Ingo, Heredia, Raul, Héron, Delphine, Isidor, Bertrand, Jonasson, Amy R., Joset, Pascal, Keren, Boris, Kok, Fernando, Kroes, Hester Y., Lavillaureix, Alinoë, Lu, Xin, Maas, Saskia M., Maegawa, Gustavo H.B., Marcelis, Carlo L.M., Mark, Paul R., Masruha, Marcelo R., McLaughlin, Heather M., McWalter, Kirsty, Melchinger, Esther U., Mercimek-Andrews, Saadet, Nava, Caroline, Pendziwiat, Manuela, Person, Richard, Ramelli, Gian Paolo, Ramos, Luiza L.P., Rauch, Anita, Reavey, Caitlin, Renieri, Alessandra, Rieß, Angelika, Sanchez-Valle, Amarilis, Sattar, Shifteh, Saunders, Carol, Schwarz, Niklas, Smol, Thomas, Srour, Myriam, Steindl, Katharina, Syrbe, Steffen, Taylor, Jenny C., Telegrafi, Aida, Thiffault, Isabelle, Trauner, Doris A., van der Linden, Helio, Jr., van Koningsbruggen, Silvana, Villard, Laurent, Vogel, Ida, Weber, Yvonne G., Wentzensen, Ingrid M., Widjaja, Elysa, Zak, Jaroslav, Baxter, Samantha, and Rodan, Lance H.
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- 2019
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23. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy
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O'Donnell-Luria, Anne H, Pais, Lynn S, Faundes, Víctor, Wood, Jordan C, Sveden, Abigail, Luria, Victor, Abou Jamra, Rami, Accogli, Andrea, Amburgey, Kimberly, Anderlid, Britt Marie, Azzarello-Burri, Silvia, Basinger, Alice A, Bianchini, Claudia, Bird, Lynne M, Buchert, Rebecca, Carre, Wilfrid, Ceulemans, Sophia, Charles, Perrine, Cox, Helen, Culliton, Lisa, Currò, Aurora, Deciphering Developmental Disorders (DDD) Study, Demurger, Florence, Dowling, James J, Duban-Bedu, Benedicte, Dubourg, Christèle, Eiset, Saga Elise, Escobar, Luis F, Ferrarini, Alessandra, Haack, Tobias B, Hashim, Mona, Heide, Solveig, Helbig, Katherine L, Helbig, Ingo, Heredia, Raul, Héron, Delphine, Isidor, Bertrand, Jonasson, Amy R, Joset, Pascal, Keren, Boris, Kok, Fernando, Kroes, Hester Y, Lavillaureix, Alinoë, Lu, Xin, Maas, Saskia M, Maegawa, Gustavo HB, Marcelis, Carlo LM, Mark, Paul R, Masruha, Marcelo R, McLaughlin, Heather M, McWalter, Kirsty, Melchinger, Esther U, Mercimek-Andrews, Saadet, Nava, Caroline, Pendziwiat, Manuela, Person, Richard, Ramelli, Gian Paolo, Ramos, Luiza LP, Rauch, Anita, Reavey, Caitlin, Renieri, Alessandra, Rieß, Angelika, Sanchez-Valle, Amarilis, Sattar, Shifteh, Saunders, Carol, Schwarz, Niklas, Smol, Thomas, Srour, Myriam, Steindl, Katharina, Syrbe, Steffen, Taylor, Jenny C, Telegrafi, Aida, Thiffault, Isabelle, Trauner, Doris A, van der Linden, Helio, van Koningsbruggen, Silvana, Villard, Laurent, Vogel, Ida, Vogt, Julie, Weber, Yvonne G, Wentzensen, Ingrid M, Widjaja, Elysa, Zak, Jaroslav, Baxter, Samantha, Banka, Siddharth, and Rodan, Lance H
- Subjects
Adult ,Male ,Heterozygote ,Adolescent ,Intellectual and Developmental Disabilities (IDD) ,Autism ,global developmental delay ,Haploinsufficiency ,Neurodegenerative ,H3K4 methylation ,Medical and Health Sciences ,Young Adult ,Clinical Research ,Deciphering Developmental Disorders (DDD) Study ,Humans ,2.1 Biological and endogenous factors ,Aetiology ,Child ,Preschool ,Pediatric ,Genetics & Heredity ,Epilepsy ,Neurosciences ,Infant ,Genetic Variation ,Biological Sciences ,neurodevelopmental disorder ,Pedigree ,KMT2E ,Brain Disorders ,DNA-Binding Proteins ,Phenotype ,epileptic encephalopathy ,Mental Health ,Neurodevelopmental Disorders ,intellectual disability ,Neurological ,Female - Abstract
We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.
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- 2019
24. De Novo Variants in the F-Box Protein FBXO11 in 20 Individuals with a Variable Neurodevelopmental Disorder
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Gregor, Anne, Sadleir, Lynette G., Asadollahi, Reza, Azzarello-Burri, Silvia, Battaglia, Agatino, Ousager, Lilian Bomme, Boonsawat, Paranchai, Bruel, Ange-Line, Buchert, Rebecca, Calpena, Eduardo, Cogné, Benjamin, Dallapiccola, Bruno, Distelmaier, Felix, Elmslie, Frances, Faivre, Laurence, Haack, Tobias B., Harrison, Victoria, Henderson, Alex, Hunt, David, Isidor, Bertrand, Joset, Pascal, Kumada, Satoko, Lachmeijer, Augusta M.A., Lees, Melissa, Lynch, Sally Ann, Martinez, Francisco, Matsumoto, Naomichi, McDougall, Carey, Mefford, Heather C., Miyake, Noriko, Myers, Candace T., Moutton, Sébastien, Nesbitt, Addie, Novelli, Antonio, Orellana, Carmen, Rauch, Anita, Rosello, Monica, Saida, Ken, Santani, Avni B., Sarkar, Ajoy, Scheffer, Ingrid E., Shinawi, Marwan, Steindl, Katharina, Symonds, Joseph D., Zackai, Elaine H., Reis, André, Sticht, Heinrich, and Zweier, Christiane
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- 2018
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25. Medizinische Genetik im ärztlichen Alltag
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Azzarello-Burri, Silvia, Rauch, Anita, and University of Zurich
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10039 Institute of Medical Genetics ,Genetics ,570 Life sciences ,biology ,610 Medicine & health ,General Medicine - Abstract
Man nimmt an, dass ca. 5–8% der Bevolkerung an einer von mindestens 6000 genetisch bedingten seltenen Erkrankungen leidet.
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- 2017
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26. Prevalence of genetic susceptibility for breast and ovarian cancer in a non-cancer related study population: secondary germline findings from a Swiss single centre cohort
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Kraemer, Dennis, primary, Azzarello-Burri, Silvia, additional, Steindl, Katharina, additional, Boonsawat, Paranchai, additional, Zweier, Markus, additional, Dedes, Konstantin J., additional, Joset, Pascal, additional, Fink, Daniel, additional, and Rauch, Anita, additional
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- 2019
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27. Prevalence of genetic susceptibility for breast and ovarian cancer in a non-cancer related study population: secondary germline findings from a Swiss single centre cohort
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Kraemer, Dennis; https://orcid.org/0000-0001-7084-2068, Azzarello-Burri, Silvia, Steindl, Katharina; https://orcid.org/0000-0002-4425-3072, Boonsawat, Paranchai, Zweier, Markus, Dedes, Konstantin J, Joset, Pascal, Fink, Daniel, Rauch, Anita, Kraemer, Dennis; https://orcid.org/0000-0001-7084-2068, Azzarello-Burri, Silvia, Steindl, Katharina; https://orcid.org/0000-0002-4425-3072, Boonsawat, Paranchai, Zweier, Markus, Dedes, Konstantin J, Joset, Pascal, Fink, Daniel, and Rauch, Anita
- Abstract
BACKGROUND Since the advent of high-throughput sequencing technologies, organised germline screening, independent of the personal and family cancer history, has been frequently proposed. Since ethnic and geographic populations significantly differ in their mutation spectra and prevalence, one critical prerequisite would be the knowledge of the expected carrier frequencies. OBJECTIVE For the first time, in a retrospective non-cancer related cohort from a single Swiss genetic centre, we systematically assessed the prevalence of secondary findings in 19 genes (BRCA1/2 plus 17 non-BRCA genes) previously designated by the US National Comprehensive Cancer Network (NCCN) for hereditary breast and ovarian cancer (HBOC) germline testing. DESIGN A total of 400 individuals without a cancer diagnosis undergoing whole-exome sequencing (WES) analysis for neurodevelopmental disorders (NDDs) from 2015 to 2017 at IMG Zurich were included after quality assessment. Among these, 180 were unaffected parental couples, 27 unaffected parental singles and 13 NDD index patients (mean age 43 years). The majority of the cohort was of Caucasian ethnicity (n = 336, 84.0%) and of Northwest European ancestry (n = 202, 50.5%), for 70 of whom (42.5%) an autochthonous Swiss descent was assumed. For WES filtering of rare, potentially actionable secondary variants in HBOC genes, an overall minor allele frequency (MAF) below 0.65% was used as cut-off. Each rare variant was manually evaluated according to the recommended ACGM-AMP standards, with some adaptations including “hypomorphic” as an additional distinct pathogenicity class. RESULTS Overall, 526 rare secondary variants (339 different variants) were encountered, with the BRCA1/2 genes accounting for 27.2% of the total variant yield. If stratified for variant pathogenicity, for BRCA1/2, three pathogenic variants were found in three females of Italian ancestry (carrier frequency of 0.8%). In the non-BRCA genes, five carriers of (likely) p
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- 2019
28. The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study
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Papuc, Sorina M, Abela, Lucia, Steindl, Katharina; https://orcid.org/0000-0002-4425-3072, Begemann, Anaïs; https://orcid.org/0000-0001-6762-0819, Simmons, Thomas L, Schmitt, Bernhard, Zweier, Markus; https://orcid.org/0000-0001-8290-0413, Oneda, Beatrice, Socher, Eileen, Crowther, Lisa M, Wohlrab, Gabriele, Gogoll, Laura, Poms, Martin, Seiler, Michelle; https://orcid.org/0000-0002-1263-5818, Papik, Michael; https://orcid.org/0009-0009-0775-2700, Baldinger, Rosa, Baumer, Alessandra, Asadollahi, Reza; https://orcid.org/0000-0002-1497-0564, Kroell-Seger, Judith, Schmid, Regula, Iff, Tobias, Schmitt-Mechelke, Thomas, Otten, Karoline, Hackenberg, Annette, Addor, Marie-Claude, Klein, Andrea, Azzarello-Burri, Silvia, Sticht, Heinrich, Joset, Pascal, Plecko, Barbara, Rauch, Anita, Papuc, Sorina M, Abela, Lucia, Steindl, Katharina; https://orcid.org/0000-0002-4425-3072, Begemann, Anaïs; https://orcid.org/0000-0001-6762-0819, Simmons, Thomas L, Schmitt, Bernhard, Zweier, Markus; https://orcid.org/0000-0001-8290-0413, Oneda, Beatrice, Socher, Eileen, Crowther, Lisa M, Wohlrab, Gabriele, Gogoll, Laura, Poms, Martin, Seiler, Michelle; https://orcid.org/0000-0002-1263-5818, Papik, Michael; https://orcid.org/0009-0009-0775-2700, Baldinger, Rosa, Baumer, Alessandra, Asadollahi, Reza; https://orcid.org/0000-0002-1497-0564, Kroell-Seger, Judith, Schmid, Regula, Iff, Tobias, Schmitt-Mechelke, Thomas, Otten, Karoline, Hackenberg, Annette, Addor, Marie-Claude, Klein, Andrea, Azzarello-Burri, Silvia, Sticht, Heinrich, Joset, Pascal, Plecko, Barbara, and Rauch, Anita
- Abstract
Early-onset epileptic encephalopathy (EE) and combined developmental and epileptic encephalopathies (DEE) are clinically and genetically heterogeneous severely devastating conditions. Recent studies emphasized de novo variants as major underlying cause suggesting a generally low-recurrence risk. In order to better understand the full genetic landscape of EE and DEE, we performed high-resolution chromosomal microarray analysis in combination with whole-exome sequencing in 63 deeply phenotyped independent patients. After bioinformatic filtering for rare variants, diagnostic yield was improved for recessive disorders by manual data curation as well as molecular modeling of missense variants and untargeted plasma-metabolomics in selected patients. In total, we yielded a diagnosis in ∼42% of cases with causative copy number variants in 6 patients (∼10%) and causative sequence variants in 16 established disease genes in 20 patients (∼32%), including compound heterozygosity for causative sequence and copy number variants in one patient. In total, 38% of diagnosed cases were caused by recessive genes, of which two cases escaped automatic calling due to one allele occurring de novo. Notably, we found the recessive gene SPATA5 causative in as much as 3% of our cohort, indicating that it may have been underdiagnosed in previous studies. We further support candidacy for neurodevelopmental disorders of four previously described genes (PIK3AP1, GTF3C3, UFC1, and WRAP53), three of which also followed a recessive inheritance pattern. Our results therefore confirm the importance of de novo causative gene variants in EE/DEE, but additionally illustrate the major role of mostly compound heterozygous or hemizygous recessive inheritance and consequently high-recurrence risk.
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- 2019
29. The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study
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Papuc, Sorina M., primary, Abela, Lucia, additional, Steindl, Katharina, additional, Begemann, Anaïs, additional, Simmons, Thomas L., additional, Schmitt, Bernhard, additional, Zweier, Markus, additional, Oneda, Beatrice, additional, Socher, Eileen, additional, Crowther, Lisa M., additional, Wohlrab, Gabriele, additional, Gogoll, Laura, additional, Poms, Martin, additional, Seiler, Michelle, additional, Papik, Michael, additional, Baldinger, Rosa, additional, Baumer, Alessandra, additional, Asadollahi, Reza, additional, Kroell-Seger, Judith, additional, Schmid, Regula, additional, Iff, Tobias, additional, Schmitt-Mechelke, Thomas, additional, Otten, Karoline, additional, Hackenberg, Annette, additional, Addor, Marie-Claude, additional, Klein, Andrea, additional, Azzarello-Burri, Silvia, additional, Sticht, Heinrich, additional, Joset, Pascal, additional, Plecko, Barbara, additional, and Rauch, Anita, additional
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- 2018
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30. Special form of osteoporosis in a 53-year-old man
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Lampart, Simon, primary, Azzarello-Burri, Silvia, additional, Henzen, Christoph, additional, and Fischli, Stefan, additional
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- 2018
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31. De Novo Variants in the F-Box Protein FBXO11 in 20 Individuals with a Variable Neurodevelopmental Disorder
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Genetica, Genetica Klinische Genetica, Gregor, Anne, Sadleir, Lynette G., Asadollahi, Reza, Azzarello-Burri, Silvia, Battaglia, Agatino, Ousager, Lilian Bomme, Boonsawat, Paranchai, Bruel, Ange Line, Buchert, Rebecca, Calpena, Eduardo, Cogné, Benjamin, Dallapiccola, Bruno, Distelmaier, Felix, Elmslie, Frances, Faivre, Laurence, Haack, Tobias B., Harrison, Victoria, Henderson, Alex, Hunt, David, Isidor, Bertrand, Joset, Pascal, Kumada, Satoko, Lachmeijer, Augusta M.A., Lees, Melissa, Lynch, Sally Ann, Martinez, Francisco, Matsumoto, Naomichi, McDougall, Carey, Mefford, Heather C., Miyake, Noriko, Myers, Candace T., Moutton, Sébastien, Nesbitt, Addie, Novelli, Antonio, Orellana, Carmen, Rauch, Anita, Rosello, Monica, Saida, Ken, Santani, Avni B., Sarkar, Ajoy, Scheffer, Ingrid E., Shinawi, Marwan, Steindl, Katharina, Symonds, Joseph D., Zackai, Elaine H., Reis, André, Sticht, Heinrich, Zweier, Christiane, DDD Study, University of Washington Center for Mendelian Genomics, Genetica, Genetica Klinische Genetica, Gregor, Anne, Sadleir, Lynette G., Asadollahi, Reza, Azzarello-Burri, Silvia, Battaglia, Agatino, Ousager, Lilian Bomme, Boonsawat, Paranchai, Bruel, Ange Line, Buchert, Rebecca, Calpena, Eduardo, Cogné, Benjamin, Dallapiccola, Bruno, Distelmaier, Felix, Elmslie, Frances, Faivre, Laurence, Haack, Tobias B., Harrison, Victoria, Henderson, Alex, Hunt, David, Isidor, Bertrand, Joset, Pascal, Kumada, Satoko, Lachmeijer, Augusta M.A., Lees, Melissa, Lynch, Sally Ann, Martinez, Francisco, Matsumoto, Naomichi, McDougall, Carey, Mefford, Heather C., Miyake, Noriko, Myers, Candace T., Moutton, Sébastien, Nesbitt, Addie, Novelli, Antonio, Orellana, Carmen, Rauch, Anita, Rosello, Monica, Saida, Ken, Santani, Avni B., Sarkar, Ajoy, Scheffer, Ingrid E., Shinawi, Marwan, Steindl, Katharina, Symonds, Joseph D., Zackai, Elaine H., Reis, André, Sticht, Heinrich, Zweier, Christiane, DDD Study, and University of Washington Center for Mendelian Genomics
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- 2018
32. Genetische Diagnostik für die Betreuung von Patientinnen mit Brustkrebs: BRCA and beyond
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Azzarello-Burri, Silvia Miranda, Niedrist, Dunja, Rauch, Anita, and University of Zurich
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10039 Institute of Medical Genetics ,Brustkrebs ,Genetics ,570 Life sciences ,biology ,610 Medicine & health ,General Medicine - Published
- 2016
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33. Analyse mutationnelle de BRCA1/2 et inhibiteurs de PARP chez les patientes atteintes de cancer de l’ovaire
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Mertz, Kirsten D., primary, Bisig, Bettina, additional, Azzarello-Burri, Silvia, additional, Rauch, Anita, additional, Röthlisberger, Benno, additional, de Laval, Laurence, additional, Cathomas, Gieri, additional, Terracciano, Luigi, additional, Jochum, Wolfram, additional, Perren, Aurel, additional, Moch, Holger, additional, Wild, Peter, additional, and Heinimann, Karel, additional
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- 2017
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34. BRCA1/2-Mutationstestung und PARP-Inhibitoren bei Patientinnen mit Ovarialkarzinom
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Mertz, Kirsten D., primary, Bisig, Bettina, additional, Azzarello-Burri, Silvia, additional, Rauch, Anita, additional, Röthlisberger, Benno, additional, de Laval, Laurence, additional, Cathomas, Gieri, additional, Terracciano, Luigi, additional, Jochum, Wolfram, additional, Perren, Aurel, additional, Moch, Holger, additional, Wild, Peter, additional, and Heinimann, Karel, additional
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- 2017
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35. MCAD-Deficiency with Severe Neonatal Onset, Fatal Outcome and Normal Acylcarnitine Profile
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Fingerhut, Ralph, primary, Joset, Pascal, additional, Rupp, Niels, additional, Girsberger, Martin, additional, Sluka, Susanna, additional, Herget, Theresia, additional, Azzarello-Burri, Silvia, additional, Rauch, Anita, additional, and Baumgartner, Matthias, additional
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- 2017
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36. C2orf71 Mutations as a Frequent Cause of Autosomal-Recessive Retinitis Pigmentosa: Clinical Analysis and Presentation of 8 Novel Mutations
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Gerth-Kahlert, Christina, primary, Tiwari, Amit, additional, Hanson, James V. M., additional, Batmanabane, Vaishnavi, additional, Traboulsi, Elias, additional, Pennesi, Mark E., additional, Al-Qahtani, Abdullah A., additional, Lam, Byron L., additional, Heckenlively, John, additional, Zweifel, Sandrine A., additional, Vincent, Ajoy, additional, Fierz, Fabienne, additional, Barthelmes, Daniel, additional, Branham, Kari, additional, Khan, Naheed, additional, Bahr, Angela, additional, Baehr, Luzy, additional, Magyar, István, additional, Koller, Samuel, additional, Azzarello-Burri, Silvia, additional, Niedrist, Dunja, additional, Heon, Elise, additional, and Berger, Wolfgang, additional
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- 2017
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37. Low-Level Chromosomal Mosaicism in Neurodevelopmental Disorders
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Oneda, Beatrice, Asadollahi, Reza, Azzarello-Burri, Silvia, Niedrist, Dunja; https://orcid.org/0000-0002-2768-9106, Baldinger, Rosa, Masood, Rahim, Schinzel, Albert, Latal, Bea; https://orcid.org/0000-0003-1309-4790, Jenni, Oskar G; https://orcid.org/0000-0002-4561-6277, Rauch, Anita, Oneda, Beatrice, Asadollahi, Reza, Azzarello-Burri, Silvia, Niedrist, Dunja; https://orcid.org/0000-0002-2768-9106, Baldinger, Rosa, Masood, Rahim, Schinzel, Albert, Latal, Bea; https://orcid.org/0000-0003-1309-4790, Jenni, Oskar G; https://orcid.org/0000-0002-4561-6277, and Rauch, Anita
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- 2017
38. C2orf71 Mutations as a Frequent Cause of Autosomal-Recessive Retinitis Pigmentosa: Clinical Analysis and Presentation of 8 Novel Mutations
- Author
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Gerth-Kahlert, Christina, Tiwari, Amit, Hanson, James V M, Batmanabane, Vaishnavi, Traboulsi, Elias, Pennesi, Mark E, Al-Qahtani, Abdullah A, Lam, Byron L, Heckenlively, John, Zweifel, Sandrine A, Vincent, Ajoy, Fierz, Fabienne, Barthelmes, Daniel, Branham, Kari, Khan, Naheed, Bahr, Angela; https://orcid.org/0000-0001-9759-2599, Baehr, Luzy, Magyar, István, Koller, Samuel, Azzarello-Burri, Silvia, Niedrist, Dunja; https://orcid.org/0000-0002-2768-9106, Heon, Elise, Berger, Wolfgang, Gerth-Kahlert, Christina, Tiwari, Amit, Hanson, James V M, Batmanabane, Vaishnavi, Traboulsi, Elias, Pennesi, Mark E, Al-Qahtani, Abdullah A, Lam, Byron L, Heckenlively, John, Zweifel, Sandrine A, Vincent, Ajoy, Fierz, Fabienne, Barthelmes, Daniel, Branham, Kari, Khan, Naheed, Bahr, Angela; https://orcid.org/0000-0001-9759-2599, Baehr, Luzy, Magyar, István, Koller, Samuel, Azzarello-Burri, Silvia, Niedrist, Dunja; https://orcid.org/0000-0002-2768-9106, Heon, Elise, and Berger, Wolfgang
- Published
- 2017
39. Medizinische Genetik im ärztlichen Alltag
- Author
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Azzarello-Burri, Silvia; https://orcid.org/0000-0001-8911-3500, Rauch, Anita; https://orcid.org/0000-0003-2930-3163, Azzarello-Burri, Silvia; https://orcid.org/0000-0001-8911-3500, and Rauch, Anita; https://orcid.org/0000-0003-2930-3163
- Abstract
Man nimmt an, dass ca. 5–8% der Bevölkerung an einer von mindestens 6000 genetisch bedingten seltenen Erkrankungen leidet. Der häufgste Zuweisungsgrund in unsere Erwachsenen-Sprechstunde ist die Frage nach dem Vorliegen einer genetisch bedingten Tumorerkrankungs-Prädisposition oder Bindegewebserkrankung. Es ist wichtig, dass Sie als betreuender Arzt eine entsprechende Veranlagung bei Patienten in Ihrer Praxis erkennen können. Dies möchten wir Ihnen anhand einiger Patientenbeispiele illustrieren.
- Published
- 2017
40. Low-Level Chromosomal Mosaicism in Neurodevelopmental Disorders
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Oneda, Beatrice, primary, Asadollahi, Reza, additional, Azzarello-Burri, Silvia, additional, Niedrist, Dunja, additional, Baldinger, Rosa, additional, Masood, Rahim, additional, Schinzel, Albert, additional, Latal, Bea, additional, Jenni, Oskar G., additional, and Rauch, Anita, additional
- Published
- 2017
- Full Text
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41. Genetische Diagnostik für die Betreuung von Patientinnen mit Brustkrebs: BRCA and beyond
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Azzarello-Burri, Silvia Miranda; https://orcid.org/0000-0001-8911-3500, Niedrist, Dunja; https://orcid.org/0000-0002-2768-9106, Rauch, Anita; https://orcid.org/0000-0003-2930-3163, Azzarello-Burri, Silvia Miranda; https://orcid.org/0000-0001-8911-3500, Niedrist, Dunja; https://orcid.org/0000-0002-2768-9106, and Rauch, Anita; https://orcid.org/0000-0003-2930-3163
- Abstract
Diese kurze Übersicht zur hereditären Brustkrebserkrankung soll illustrieren, wie wichtig es ist, Patienten mit erhöhtem Erkrankungsrisiko zu identifizieren und den Betroffenen, falls gewünscht, eine genetische Testung anzubieten, um den Patienten und auch deren Verwandten die bestmögliche individuelle Betreuung zu bieten. Ein Schritt Richtung personalisierter Medizin!
- Published
- 2016
42. Horizontal Gaze Palsy in Two Brothers with Compound Heterozygous ROBO3 Gene Mutations
- Author
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Boltshauser, Eugen, primary, Gerth-Kahlert, Christina, primary, Stahr, Nikolai, primary, Azzarello-Burri, Silvia, primary, Plecko, Barbara, primary, and Hackenberg, Annette, additional
- Published
- 2016
- Full Text
- View/download PDF
43. Genetik: Genetische Diagnostik für die Betreuung von Patientinnen mit Brustkrebs: BRCA and beyond
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Azzarello-Burri, Silvia Miranda, primary, Niedrist, Dunja, additional, and Rauch, Anita, additional
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- 2016
- Full Text
- View/download PDF
44. Génétique: Diagnostic génétique pour la prise en charge des patientes atteintes de cancer du sein: BRCA et au-delà
- Author
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Azzarello-Burri, Silvia Miranda, primary, Niedrist, Dunja, additional, and Rauch, Anita, additional
- Published
- 2016
- Full Text
- View/download PDF
45. De novo missense mutations in the NAA10 gene cause severe non-syndromic developmental delay in males and females
- Author
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Popp, Bernt, Støve, Svein I, Endele, Sabine, Myklebust, Line M, Hoyer, Juliane, Sticht, Heinrich, Azzarello-Burri, Silvia, Rauch, Anita, Arnesen, Thomas, Reis, André, Popp, Bernt, Støve, Svein I, Endele, Sabine, Myklebust, Line M, Hoyer, Juliane, Sticht, Heinrich, Azzarello-Burri, Silvia, Rauch, Anita, Arnesen, Thomas, and Reis, André
- Abstract
Recent studies revealed the power of whole-exome sequencing to identify mutations in sporadic cases with non-syndromic intellectual disability. We now identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay but without any major dysmorphism by trio whole-exome sequencing. Both de novo variants were predicted to be deleterious, and we excluded other variants in this gene. This X-linked gene encodes N-alpha-acetyltransferase 10, the catalytic subunit of the NatA complex involved in multiple cellular processes. A single hypomorphic missense variant p.(Ser37Pro) was previously associated with Ogden syndrome in eight affected males from two different families. This rare disorder is characterized by a highly recognizable phenotype, global developmental delay and results in death during infancy. In an attempt to explain the discrepant phenotype, we used in vitro N-terminal acetylation assays which suggested that the severity of the phenotype correlates with the remaining catalytic activity. The variant in the Ogden syndrome patients exhibited a lower activity than the one seen in the boy with intellectual disability, while the variant in the girl was the most severe exhibiting only residual activity in the acetylation assays used. We propose that N-terminal acetyltransferase deficiency is clinically heterogeneous with the overall catalytic activity determining the phenotypic severity.
- Published
- 2015
46. De novo missense mutations in the NAA10 gene cause severe non-syndromic developmental delay in males and females
- Author
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Popp, Bernt, primary, Støve, Svein I, additional, Endele, Sabine, additional, Myklebust, Line M, additional, Hoyer, Juliane, additional, Sticht, Heinrich, additional, Azzarello-Burri, Silvia, additional, Rauch, Anita, additional, Arnesen, Thomas, additional, and Reis, André, additional
- Published
- 2014
- Full Text
- View/download PDF
47. Clinical and experimental evidence suggest a link between KIF7and C5orf42-related ciliopathies through Sonic Hedgehog signaling
- Author
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Asadollahi, Reza, Strauss, Justin, Zenker, Martin, Beuing, Oliver, Edvardson, Simon, Elpeleg, Orly, Strom, Tim, Joset, Pascal, Niedrist, Dunja, Otte, Christine, Oneda, Beatrice, Boonsawat, Paranchai, Azzarello-Burri, Silvia, Bartholdi, Deborah, Papik, Michael, Zweier, Markus, Haas, Cordula, Ekici, Arif, Baumer, Alessandra, Boltshauser, Eugen, Steindl, Katharina, Nothnagel, Michael, Schinzel, Albert, Stoeckli, Esther, and Rauch, Anita
- Abstract
Acrocallosal syndrome (ACLS) is an autosomal recessive neurodevelopmental disorder caused by KIF7defects and belongs to the heterogeneous group of ciliopathies related to Joubert syndrome (JBTS). While ACLS is characterized by macrocephaly, prominent forehead, depressed nasal bridge, and hypertelorism, facial dysmorphism has not been emphasized in JBTS cohorts with molecular diagnosis. To evaluate the specificity and etiology of ACLS craniofacial features, we performed whole exome or targeted Sanger sequencing in patients with the aforementioned overlapping craniofacial appearance but variable additional ciliopathy features followed by functional studies. We found (likely) pathogenic variants of KIF7in 5 out of 9 families, including the original ACLS patients, and delineated 1000 to 4000-year-old Swiss founder alleles. Three of the remaining families had (likely) pathogenic variants in the JBTS gene C5orf42, and one patient had a novel de novo frameshift variant in SHHknown to cause autosomal dominant holoprosencephaly. In accordance with the patients’ craniofacial anomalies, we showed facial midline widening after silencing of C5orf42in chicken embryos. We further supported the link between KIF7, SHH, and C5orf42 by demonstrating abnormal primary cilia and diminished response to a SHH agonist in fibroblasts of C5orf42-mutated patients, as well as axonal pathfinding errors in C5orf42-silenced chicken embryos similar to those observed after perturbation of Shh signaling. Our findings, therefore, suggest that beside the neurodevelopmental features, macrocephaly and facial widening are likely more general signs of disturbed SHH signaling. Nevertheless, long-term follow-up revealed that C5orf42-mutated patients showed catch-up development and fainting of facial features contrary to KIF7-mutated patients.
- Published
- 2018
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48. Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability
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Asadollahi, Reza, primary, Oneda, Beatrice, additional, Sheth, Frenny, additional, Azzarello-Burri, Silvia, additional, Baldinger, Rosa, additional, Joset, Pascal, additional, Latal, Beatrice, additional, Knirsch, Walter, additional, Desai, Soaham, additional, Baumer, Alessandra, additional, Houge, Gunnar, additional, Andrieux, Joris, additional, and Rauch, Anita, additional
- Published
- 2013
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49. Hemizygous deletion of COL3A1, COL5A2, and MSTN causes a complex phenotype with aortic dissection: a lesson for and from true haploinsufficiency
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Meienberg, Janine, primary, Rohrbach, Marianne, additional, Neuenschwander, Stefan, additional, Spanaus, Katharina, additional, Giunta, Cecilia, additional, Alonso, Sira, additional, Arnold, Eliane, additional, Henggeler, Caroline, additional, Regenass, Stephan, additional, Patrignani, Andrea, additional, Azzarello-Burri, Silvia, additional, Steiner, Bernhard, additional, Nygren, Anders OH, additional, Carrel, Thierry, additional, Steinmann, Beat, additional, and Mátyás, Gábor, additional
- Published
- 2010
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50. Goltz–Gorlin (focal dermal hypoplasia) and the microphthalmia with linear skin defects (MLS) syndrome: no evidence of genetic overlap
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Harmsen, May-Britt, primary, Azzarello-Burri, Silvia, additional, García González, M Mar, additional, Gillessen-Kaesbach, Gabriele, additional, Meinecke, Peter, additional, Müller, Dietmar, additional, Rauch, Anita, additional, Rossier, Eva, additional, Seemanova, Eva, additional, Spaich, Christiane, additional, Steiner, Bernhard, additional, Wieczorek, Dagmar, additional, Zenker, Martin, additional, and Kutsche, Kerstin, additional
- Published
- 2009
- Full Text
- View/download PDF
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