189 results on '"Herkert, Johanna C."'
Search Results
2. Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study
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Jansen, Mark, de Brouwer, Remco, Hassanzada, Fahima, Schoemaker, Angela E., Schmidt, Amand F., Kooijman-Reumerman, Maria D., Bracun, Valentina, Slieker, Martijn G., Dooijes, Dennis, Vermeer, Alexa M.C., Wilde, Arthur A.M., Amin, Ahmad S., Lekanne Deprez, Ronald H., Herkert, Johanna C., Christiaans, Imke, de Boer, Rudolf A., Jongbloed, Jan D.H., van Tintelen, J. Peter, Asselbergs, Folkert W., and Baas, Annette F.
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- 2024
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3. Further clinical and molecular characterization of an XLID syndrome associated with BRWD3 variants, a gene implicated in the leukemia-related JAK-STAT pathway
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Delanne, Julian, Lecat, Magaly, Blackburn, Patrick R., Klee, Eric W., Stumpel, Constance T.R.M., Stegmann, Sander, Stevens, Servi J.C., Nava, Caroline, Heron, Delphine, Keren, Boris, Mahida, Sonal, Naidu, Sakkubai, Babovic-Vuksanovic, Dusica, Herkert, Johanna C., Torring, Pernille M., Kibæk, Maria, De Bie, Isabelle, Pfundt, Rolph, Hendriks, Yvonne M.C., Ousager, Lilian Bomme, Bend, Renee, Warren, Hannah, Skinner, Steven A., Lyons, Michael J., Pöe, Charlotte, Chevarin, Martin, Jouan, Thibaud, Garde, Aurore, Thomas, Quentin, Kuentz, Paul, Tisserant, Emilie, Duffourd, Yannis, Philippe, Christophe, Faivre, Laurence, and Thauvin-Robinet, Christel
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- 2023
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4. De novo, deleterious sequence variants that alter the transcriptional activity of the homeoprotein PBX1 are associated with intellectual disability and pleiotropic developmental defects
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Slavotinek, Anne, Risolino, Maurizio, Losa, Marta, Cho, Megan T, Monaghan, Kristin G, Schneidman-Duhovny, Dina, Parisotto, Sarah, Herkert, Johanna C, Stegmann, Alexander PA, Miller, Kathryn, Shur, Natasha, Chui, Jacqueline, Muller, Eric, DeBrosse, Suzanne, Szot, Justin O, Chapman, Gavin, Pachter, Nicholas S, Winlaw, David S, Mendelsohn, Bryce A, Dalton, Joline, Sarafoglou, Kyriakie, Karachunski, Peter I, Lewis, Jane M, Pedro, Helio, Dunwoodie, Sally L, Selleri, Licia, and Shieh, Joseph
- Subjects
Congenital Structural Anomalies ,Pediatric ,Stem Cell Research ,Clinical Research ,Genetics ,Stem Cell Research - Embryonic - Non-Human ,Kidney Disease ,Biotechnology ,2.1 Biological and endogenous factors ,Aetiology ,Adolescent ,Adult ,Amino Acid Sequence ,Animals ,Child ,Child ,Preschool ,Female ,Genetic Pleiotropy ,Homeodomain Proteins ,Humans ,Infant ,Infant ,Newborn ,Intellectual Disability ,Male ,Mice ,Pre-B-Cell Leukemia Transcription Factor 1 ,Pregnancy ,Protein Binding ,Proto-Oncogene Proteins ,Transcription Factors ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
We present eight patients with de novo, deleterious sequence variants in the PBX1 gene. PBX1 encodes a three amino acid loop extension (TALE) homeodomain transcription factor that forms multimeric complexes with TALE and HOX proteins to regulate target gene transcription during development. As previously reported, Pbx1 homozygous mutant mice (Pbx1-/-) develop malformations and hypoplasia or aplasia of multiple organs, including the craniofacial skeleton, ear, branchial arches, heart, lungs, diaphragm, gut, kidneys, and gonads. Clinical findings similar to those in Pbx mutant mice were observed in all patients with varying expressivity and severity, including external ear anomalies, abnormal branchial arch derivatives, heart malformations, diaphragmatic hernia, renal hypoplasia and ambiguous genitalia. All patients but one had developmental delays. Previously reported patients with congenital anomalies affecting the kidney and urinary tract exhibited deletions and loss of function variants in PBX1. The sequence variants in our cases included missense substitutions adjacent to the PBX1 homeodomain (p.Arg184Pro, p.Met224Lys, and p.Arg227Pro) or within the homeodomain (p.Arg234Pro, and p.Arg235Gln), whereas p.Ser262Glnfs*2, and p.Arg288* yielded truncated PBX1 proteins. Functional studies on five PBX1 sequence variants revealed perturbation of intrinsic, PBX-dependent transactivation ability and altered nuclear translocation, suggesting abnormal interactions between mutant PBX1 proteins and wild-type TALE or HOX cofactors. It is likely that the mutations directly affect the transcription of PBX1 target genes to impact embryonic development. We conclude that deleterious sequence variants in PBX1 cause intellectual disability and pleiotropic malformations resembling those in Pbx1 mutant mice, arguing for strong conservation of gene function between these two species.
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- 2017
5. Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study
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Onderzoek Precision medicine, Genetica Klinische Genetica, Cardiologie patientenzorg, Child Health, Circulatory Health, Genetica Sectie Genoomdiagnostiek, Genetica Groep Van Tintelen, Cancer, Team Medisch, Jansen, Mark, de Brouwer, Remco, Hassanzada, Fahima, Schoemaker, Angela E, Schmidt, Amand F, Kooijman-Reumerman, Maria D, Bracun, Valentina, Slieker, Martijn G, Dooijes, Dennis, Vermeer, Alexa M C, Wilde, Arthur A M, Amin, Ahmad S, Lekanne Deprez, Ronald H, Herkert, Johanna C, Christiaans, Imke, de Boer, Rudolf A, Jongbloed, Jan D H, van Tintelen, J Peter, Asselbergs, Folkert W, Baas, Annette F, Onderzoek Precision medicine, Genetica Klinische Genetica, Cardiologie patientenzorg, Child Health, Circulatory Health, Genetica Sectie Genoomdiagnostiek, Genetica Groep Van Tintelen, Cancer, Team Medisch, Jansen, Mark, de Brouwer, Remco, Hassanzada, Fahima, Schoemaker, Angela E, Schmidt, Amand F, Kooijman-Reumerman, Maria D, Bracun, Valentina, Slieker, Martijn G, Dooijes, Dennis, Vermeer, Alexa M C, Wilde, Arthur A M, Amin, Ahmad S, Lekanne Deprez, Ronald H, Herkert, Johanna C, Christiaans, Imke, de Boer, Rudolf A, Jongbloed, Jan D H, van Tintelen, J Peter, Asselbergs, Folkert W, and Baas, Annette F
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- 2024
6. Contiguous Gene Deletion of Chromosome 15q25.2q25.3 in Biallelic ALPK3 -Related Cardiomyopathy: Novel Insights Into Phenotypic Presentation and Variant Spectrum
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Grutters, Laura A., primary, Klein Wassink-Ruiter, Jolien S., additional, Dijkhuizen, Trijnie, additional, Nijenhuis, Hessel P., additional, Jongbloed, Jan D.H., additional, and Herkert, Johanna C., additional
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- 2023
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7. The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome
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van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Wödl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F. J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W. Y., Chung, Brain H. Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hülya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, López-González, Vanesa, Maas, Saskia, Mancini, Grazia M. S., Marcelis, Carlo, Martinez, Francisco, Maystadt, Isabelle, McGuire, Marianne, McKee, Shane, Mehta, Sarju, Metcalfe, Kay, Milunsky, Jeff, Mizuno, Seiji, Moeschler, John B., Netzer, Christian, Ockeloen, Charlotte W., Oehl-Jaschkowitz, Barbara, Okamoto, Nobuhiko, Olminkhof, Sharon N. M., Orellana, Carmen, Pasquier, Laurent, Pottinger, Caroline, Riehmer, Vera, Robertson, Stephen P., Roifman, Maian, Rooryck, Caroline, Ropers, Fabienne G., Rosello, Monica, Ruivenkamp, Claudia A. L., Sagiroglu, Mahmut S., Sallevelt, Suzanne C. E. H., Sanchis Calvo, Amparo, Simsek-Kiper, Pelin O., Soares, Gabriela, Solaeche, Lucia, Sonmez, Fatma Mujgan, Splitt, Miranda, Steenbeek, Duco, Stegmann, Alexander P. A., Stumpel, Constance T. R. M., Tanabe, Saori, Uctepe, Eyyup, Utine, G. Eda, Veenstra-Knol, Hermine E., Venkateswaran, Sunita, Vilain, Catheline, Vincent-Delorme, Catherine, Vulto-van Silfhout, Anneke T., Wheeler, Patricia, Wilson, Golder N., Wilson, Louise C., Wollnik, Bernd, Kosho, Tomoki, Wieczorek, Dagmar, Eichler, Evan, Pfundt, Rolph, de Vries, Bert B. A., Clayton-Smith, Jill, and Santen, Gijs W. E.
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- 2019
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8. Abstract P391: Cellular Camp Nanoarchtecture-signaling Changes Cause Hypertension With Brachydactyly
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Kayser, Charlotte, primary, Leeuwen, Lisette, additional, Herkert, Johanna C, additional, Vos, Yvonne J, additional, Lohse, Martin, additional, Luft, Friedrich C, additional, and Bock, Andreas, additional
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- 2023
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9. Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies
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Jansen, Mark, primary, de Brouwer, Remco, additional, Hassanzada, Fahima, additional, Schoemaker, Angela E., additional, Schmidt, Amand F., additional, Kooijman-Reumerman, Maria D., additional, Bracun, Valentina, additional, Slieker, Martijn G., additional, Dooijes, Dennis, additional, Vermeer, Alexa M.C., additional, Wilde, Arthur A.M., additional, Amin, Ahmad S., additional, Lekanne Deprez, Ronald H., additional, Herkert, Johanna C., additional, Christiaans, Imke, additional, de Boer, Rudolf A., additional, Jongbloed, Jan D.H., additional, van Tintelen, J. Peter, additional, Asselbergs, Folkert W., additional, and Baas, Annette F., additional
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- 2023
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10. Toward an effective exome-based genetic testing strategy in pediatric dilated cardiomyopathy
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Herkert, Johanna C, Abbott, Kristin M, Birnie, Erwin, Meems-Veldhuis, Martine T, Boven, Ludolf G, Benjamins, Marloes, du Marchie Sarvaas, Gideon J, Barge-Schaapveld, Daniela Q C M, van Tintelen, J Peter, van der Zwaag, Paul A, Vos, Yvonne J, Sinke, Richard J, van den Berg, Maarten P, van Langen, Irene M, and Jongbloed, Jan D H
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- 2018
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11. Loss-of-function variants inCUL3cause a syndromic neurodevelopmental disorder
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Blackburn, Patrick R., primary, Ebstein, Frédéric, additional, Hsieh, Tzung-Chien, additional, Motta, Marialetizia, additional, Radio, Francesca Clementina, additional, Herkert, Johanna C., additional, Rinne, Tuula, additional, Thiffault, Isabelle, additional, Rapp, Michele, additional, Alders, Mariel, additional, Maas, Saskia, additional, Gerard, Bénédicte, additional, Smol, Thomas, additional, Vincent-Delorme, Catherine, additional, Cogné, Benjamin, additional, Isidor, Bertrand, additional, Vincent, Marie, additional, Bachmann-Gagescu, Ruxandra, additional, Rauch, Anita, additional, Joset, Pascal, additional, Ferrero, Giovanni Battista, additional, Ciolfi, Andrea, additional, Husson, Thomas, additional, Guerrot, Anne-Marie, additional, Bacino, Carlos, additional, Macmurdo, Colleen, additional, Thompson, Stephanie S., additional, Rosenfeld, Jill A., additional, Faivre, Laurence, additional, Mau-Them, Frederic Tran, additional, Deb, Wallid, additional, Vignard, Virginie, additional, Agrawal, Pankaj B., additional, Madden, Jill A., additional, Goldenberg, Alice, additional, Lecoquierre, François, additional, Zech, Michael, additional, Prokisch, Holger, additional, Necpál, Ján, additional, Jech, Robert, additional, Winkelmann, Juliane, additional, Koprušáková, Monika Turčanová, additional, Konstantopoulou, Vassiliki, additional, Younce, John R., additional, Shinawi, Marwan, additional, Mighton, Chloe, additional, Fung, Charlotte, additional, Morel, Chantal, additional, Ellis, Jordan Lerner-, additional, DiTroia, Stephanie, additional, Barth, Magalie, additional, Bonneau, Dominique, additional, Krapels, Ingrid, additional, Stegmann, Sander, additional, Schoot, Vyne van der, additional, Brunet, Theresa, additional, Bußmann, Cornelia, additional, Mignot, Cyril, additional, Courtin, Thomas, additional, Ravelli, Claudia, additional, Keren, Boris, additional, Ziegler, Alban, additional, Hasadsri, Linda, additional, Pichurin, Pavel N., additional, Klee, Eric W., additional, Grand, Katheryn, additional, Sanchez-Lara, Pedro A., additional, Krüger, Elke, additional, Bézieau, Stéphane, additional, Klinkhammer, Hannah, additional, Krawitz, Peter Michael, additional, Eichler, Evan E., additional, Tartaglia, Marco, additional, Küry, Sébastien, additional, and Wang, Tianyun, additional
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- 2023
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12. POU3F3‐related disorder: Defining the phenotype and expanding the molecular spectrum
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Rossi, Alessandra, primary, Blok, Lot Snijders, additional, Neuser, Sonja, additional, Klöckner, Chiara, additional, Platzer, Konrad, additional, Faivre, Laurence Olivier, additional, Weigand, Heike, additional, Dentici, Maria L., additional, Tartaglia, Marco, additional, Niceta, Marcello, additional, Alfieri, Paolo, additional, Srivastava, Siddharth, additional, Coulter, David, additional, Smith, Lacey, additional, Vinorum, Kristin, additional, Cappuccio, Gerarda, additional, Brunetti‐Pierri, Nicola, additional, Torun, Deniz, additional, Arslan, Mutluay, additional, Lauridsen, Mathilde F., additional, Murch, Oliver, additional, Irving, Rachel, additional, Lynch, Sally A., additional, Mehta, Sarju G., additional, Carmichael, Jenny, additional, Zonneveld‐Huijssoon, Evelien, additional, de Vries, Bert, additional, Kleefstra, Tjitske, additional, Johannesen, Katrine M., additional, Westphall, Ian T., additional, Hughes, Susan S., additional, Smithson, Sarah, additional, Evans, Julie, additional, Dudding‐Byth, Tracy, additional, Simon, Marleen, additional, van Binsbergen, Ellen, additional, Herkert, Johanna C., additional, Beunders, Gea, additional, Oppermann, Henry, additional, Bakal, Mert, additional, Møller, Rikke S., additional, Rubboli, Guido, additional, and Bayat, Allan, additional
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- 2023
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13. Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes
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Levitin, Maria O., Rawlins, Lettie E., Sanchez-Andrade, Gabriela, Arshad, Osama A., Collins, Stephan C., Sawiak, Stephen J., Iffland, Phillip H., Andersson, Malin H.L., Bupp, Caleb, Cambridge, Emma L., Coomber, Eve L., Ellis, Ian, Herkert, Johanna C., Ironfield, Holly, Jory, Logan, Kretz, Perrine F., Kant, Sarina G., Neaverson, Alexandra, Nibbeling, Esther, Rowley, Christine, Relton, Emily, Sanderson, Mark, Scott, Ethan M., Stewart, Helen, Shuen, Andrew Y., Schreiber, John, Tuck, Liz, Tonks, James, Terkelsen, Thorkild, van Ravenswaaij-Arts, Conny, Vasudevan, Pradeep, Wenger, Olivia, Wright, Michael, Day, Andrew, Hunter, Adam, Patel, Minal, Lelliott, Christopher J., Crino, Peter B., Yalcin, Binnaz, Crosby, Andrew H., Baple, Emma L., Logan, Darren W., Hurles, Matthew E., Gerety, Sebastian S., Levitin, Maria O., Rawlins, Lettie E., Sanchez-Andrade, Gabriela, Arshad, Osama A., Collins, Stephan C., Sawiak, Stephen J., Iffland, Phillip H., Andersson, Malin H.L., Bupp, Caleb, Cambridge, Emma L., Coomber, Eve L., Ellis, Ian, Herkert, Johanna C., Ironfield, Holly, Jory, Logan, Kretz, Perrine F., Kant, Sarina G., Neaverson, Alexandra, Nibbeling, Esther, Rowley, Christine, Relton, Emily, Sanderson, Mark, Scott, Ethan M., Stewart, Helen, Shuen, Andrew Y., Schreiber, John, Tuck, Liz, Tonks, James, Terkelsen, Thorkild, van Ravenswaaij-Arts, Conny, Vasudevan, Pradeep, Wenger, Olivia, Wright, Michael, Day, Andrew, Hunter, Adam, Patel, Minal, Lelliott, Christopher J., Crino, Peter B., Yalcin, Binnaz, Crosby, Andrew H., Baple, Emma L., Logan, Darren W., Hurles, Matthew E., and Gerety, Sebastian S.
- Abstract
Models
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- 2023
14. POU3F3-related disorder: Defining the phenotype and expanding the molecular spectrum
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Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Child Health, Rossi, Alessandra, Blok, Lot Snijders, Neuser, Sonja, Klöckner, Chiara, Platzer, Konrad, Faivre, Laurence Olivier, Weigand, Heike, Dentici, Maria L, Tartaglia, Marco, Niceta, Marcello, Alfieri, Paolo, Srivastava, Siddharth, Coulter, David, Smith, Lacey, Vinorum, Kristin, Cappuccio, Gerarda, Brunetti-Pierri, Nicola, Torun, Deniz, Arslan, Mutluay, Lauridsen, Mathilde F, Murch, Oliver, Irving, Rachel, Lynch, Sally A, Mehta, Sarju G, Carmichael, Jenny, Zonneveld-Huijssoon, Evelien, de Vries, Bert, Kleefstra, Tjitske, Johannesen, Katrine M, Westphall, Ian T, Hughes, Susan S, Smithson, Sarah, Evans, Julie, Dudding-Byth, Tracy, Simon, Marleen, van Binsbergen, Ellen, Herkert, Johanna C, Beunders, Gea, Oppermann, Henry, Bakal, Mert, Møller, Rikke S, Rubboli, Guido, Bayat, Allan, Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Child Health, Rossi, Alessandra, Blok, Lot Snijders, Neuser, Sonja, Klöckner, Chiara, Platzer, Konrad, Faivre, Laurence Olivier, Weigand, Heike, Dentici, Maria L, Tartaglia, Marco, Niceta, Marcello, Alfieri, Paolo, Srivastava, Siddharth, Coulter, David, Smith, Lacey, Vinorum, Kristin, Cappuccio, Gerarda, Brunetti-Pierri, Nicola, Torun, Deniz, Arslan, Mutluay, Lauridsen, Mathilde F, Murch, Oliver, Irving, Rachel, Lynch, Sally A, Mehta, Sarju G, Carmichael, Jenny, Zonneveld-Huijssoon, Evelien, de Vries, Bert, Kleefstra, Tjitske, Johannesen, Katrine M, Westphall, Ian T, Hughes, Susan S, Smithson, Sarah, Evans, Julie, Dudding-Byth, Tracy, Simon, Marleen, van Binsbergen, Ellen, Herkert, Johanna C, Beunders, Gea, Oppermann, Henry, Bakal, Mert, Møller, Rikke S, Rubboli, Guido, and Bayat, Allan
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- 2023
15. Loss-of-function variants in CUL3 cause a syndromic neurodevelopmental disorder
- Author
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Blackburn, Patrick R; https://orcid.org/0000-0003-0658-1275, Ebstein, Frédéric, Hsieh, Tzung-Chien, Motta, Marialetizia; https://orcid.org/0000-0001-6592-910X, Radio, Francesca Clementina; https://orcid.org/0000-0003-1993-8018, Herkert, Johanna C; https://orcid.org/0000-0003-0461-9102, Rinne, Tuula, Thiffault, Isabelle, Rapp, Michele, Alders, Mariel, Maas, Saskia, Gérard, Bénédicte, Smol, Thomas; https://orcid.org/0000-0002-0119-5896, Vincent-Delorme, Catherine, Cogné, Benjamin; https://orcid.org/0000-0002-5503-6292, Isidor, Bertrand, Vincent, Marie, Bachmann-Gagescu, Ruxandra; https://orcid.org/0000-0002-3571-5271, Rauch, Anita; https://orcid.org/0000-0003-2930-3163, Joset, Pascal; https://orcid.org/0000-0002-4349-9951, Ferrero, Giovanni Battista; https://orcid.org/0000-0002-3793-5788, Ciolfi, Andrea; https://orcid.org/0000-0002-6191-0978, Husson, Thomas; https://orcid.org/0000-0002-4088-5021, Guerrot, Anne-Marie, Bacino, Carlos; https://orcid.org/0000-0002-4342-5012, Macmurdo, Colleen, Thompson, Stephanie S, Rosenfeld, Jill A; https://orcid.org/0000-0001-5664-7987, Faivre, Laurence; https://orcid.org/0000-0001-9770-444X, Mau-Them, Frederic Tran; https://orcid.org/0000-0002-3795-9456, et al, Blackburn, Patrick R; https://orcid.org/0000-0003-0658-1275, Ebstein, Frédéric, Hsieh, Tzung-Chien, Motta, Marialetizia; https://orcid.org/0000-0001-6592-910X, Radio, Francesca Clementina; https://orcid.org/0000-0003-1993-8018, Herkert, Johanna C; https://orcid.org/0000-0003-0461-9102, Rinne, Tuula, Thiffault, Isabelle, Rapp, Michele, Alders, Mariel, Maas, Saskia, Gérard, Bénédicte, Smol, Thomas; https://orcid.org/0000-0002-0119-5896, Vincent-Delorme, Catherine, Cogné, Benjamin; https://orcid.org/0000-0002-5503-6292, Isidor, Bertrand, Vincent, Marie, Bachmann-Gagescu, Ruxandra; https://orcid.org/0000-0002-3571-5271, Rauch, Anita; https://orcid.org/0000-0003-2930-3163, Joset, Pascal; https://orcid.org/0000-0002-4349-9951, Ferrero, Giovanni Battista; https://orcid.org/0000-0002-3793-5788, Ciolfi, Andrea; https://orcid.org/0000-0002-6191-0978, Husson, Thomas; https://orcid.org/0000-0002-4088-5021, Guerrot, Anne-Marie, Bacino, Carlos; https://orcid.org/0000-0002-4342-5012, Macmurdo, Colleen, Thompson, Stephanie S, Rosenfeld, Jill A; https://orcid.org/0000-0001-5664-7987, Faivre, Laurence; https://orcid.org/0000-0001-9770-444X, Mau-Them, Frederic Tran; https://orcid.org/0000-0002-3795-9456, and et al
- Abstract
Purpose De novovariants inCUL3(Cullin-3 ubiquitin ligase) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here we aimed to collect sporadic cases carrying rare variants inCUL3,describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism.MethodsGenetic data and detailed clinical records were collected via multi-center collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient-derived T-cells.ResultsWe assembled a cohort of 35 individuals with heterozygousCUL3variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 33 have loss-of-function (LoF) and two have missense variants.CUL3LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin-protein conjugatesin vitro. Specifically, we show that cyclin E1 (CCNE1) and 4E-BP1 (EIF4EBP1), two prominent substrates of CUL3, fail to be targeted for proteasomal degradation in patient-derived cells.ConclusionOur study further refines the clinical and mutational spectrum ofCUL3-associated NDDs, expands the spectrum of cullin RING E3 ligase-associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism.
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- 2023
16. POU3F3-related disorder:Defining the phenotype and expanding the molecular spectrum
- Author
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Rossi, Alessandra, Blok, Lot Snijders, Neuser, Sonja, Klöckner, Chiara, Platzer, Konrad, Faivre, Laurence Olivier, Weigand, Heike, Dentici, Maria L., Tartaglia, Marco, Niceta, Marcello, Alfieri, Paolo, Srivastava, Siddharth, Coulter, David, Smith, Lacey, Vinorum, Kristin, Cappuccio, Gerarda, Brunetti-Pierri, Nicola, Torun, Deniz, Arslan, Mutluay, Lauridsen, Mathilde F., Murch, Oliver, Irving, Rachel, Lynch, Sally A., Mehta, Sarju G., Carmichael, Jenny, Zonneveld-Huijssoon, Evelien, de Vries, Bert, Kleefstra, Tjitske, Johannesen, Katrine M., Westphall, Ian T., Hughes, Susan S., Smithson, Sarah, Evans, Julie, Dudding-Byth, Tracy, Simon, Marleen, van Binsbergen, Ellen, Herkert, Johanna C., Beunders, Gea, Oppermann, Henry, Bakal, Mert, Møller, Rikke S., Rubboli, Guido, Bayat, Allan, Rossi, Alessandra, Blok, Lot Snijders, Neuser, Sonja, Klöckner, Chiara, Platzer, Konrad, Faivre, Laurence Olivier, Weigand, Heike, Dentici, Maria L., Tartaglia, Marco, Niceta, Marcello, Alfieri, Paolo, Srivastava, Siddharth, Coulter, David, Smith, Lacey, Vinorum, Kristin, Cappuccio, Gerarda, Brunetti-Pierri, Nicola, Torun, Deniz, Arslan, Mutluay, Lauridsen, Mathilde F., Murch, Oliver, Irving, Rachel, Lynch, Sally A., Mehta, Sarju G., Carmichael, Jenny, Zonneveld-Huijssoon, Evelien, de Vries, Bert, Kleefstra, Tjitske, Johannesen, Katrine M., Westphall, Ian T., Hughes, Susan S., Smithson, Sarah, Evans, Julie, Dudding-Byth, Tracy, Simon, Marleen, van Binsbergen, Ellen, Herkert, Johanna C., Beunders, Gea, Oppermann, Henry, Bakal, Mert, Møller, Rikke S., Rubboli, Guido, and Bayat, Allan
- Abstract
POU3F3 variants cause developmental delay, behavioral problems, hypotonia and dysmorphic features. We investigated the phenotypic and genetic landscape, and genotype–phenotype correlations in individuals with POU3F3-related disorders. We recruited unpublished individuals with POU3F3 variants through international collaborations and obtained updated clinical data on previously published individuals. Trio exome sequencing or single exome sequencing followed by segregation analysis were performed in the novel cohort. Functional effects of missense variants were investigated with 3D protein modeling. We included 28 individuals (5 previously published) from 26 families carrying POU3F3 variants; 23 de novo and one inherited from an affected parent. Median age at study inclusion was 7.4 years. All had developmental delay mainly affecting speech, behavioral difficulties, psychiatric comorbidities and dysmorphisms. Additional features included gastrointestinal comorbidities, hearing loss, ophthalmological anomalies, epilepsy, sleep disturbances and joint hypermobility. Autism, hearing and eye comorbidities, dysmorphisms were more common in individuals with truncating variants, whereas epilepsy was only associated with missense variants. In silico structural modeling predicted that all (likely) pathogenic variants destabilize the DNA-binding region of POU3F3. Our study refined the phenotypic and genetic landscape of POU3F3-related disorders, it reports the functional properties of the identified pathogenic variants, and delineates some genotype–phenotype correlations., POU3F3 variants cause developmental delay, behavioral problems, hypotonia and dysmorphic features. We investigated the phenotypic and genetic landscape, and genotype–phenotype correlations in individuals with POU3F3-related disorders. We recruited unpublished individuals with POU3F3 variants through international collaborations and obtained updated clinical data on previously published individuals. Trio exome sequencing or single exome sequencing followed by segregation analysis were performed in the novel cohort. Functional effects of missense variants were investigated with 3D protein modeling. We included 28 individuals (5 previously published) from 26 families carrying POU3F3 variants; 23 de novo and one inherited from an affected parent. Median age at study inclusion was 7.4 years. All had developmental delay mainly affecting speech, behavioral difficulties, psychiatric comorbidities and dysmorphisms. Additional features included gastrointestinal comorbidities, hearing loss, ophthalmological anomalies, epilepsy, sleep disturbances and joint hypermobility. Autism, hearing and eye comorbidities, dysmorphisms were more common in individuals with truncating variants, whereas epilepsy was only associated with missense variants. In silico structural modeling predicted that all (likely) pathogenic variants destabilize the DNA-binding region of POU3F3. Our study refined the phenotypic and genetic landscape of POU3F3-related disorders, it reports the functional properties of the identified pathogenic variants, and delineates some genotype–phenotype correlations.
- Published
- 2023
17. Loss-of-function variants in CUL3 cause a syndromic neurodevelopmental disorder
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Blackburn, Patrick R., Ebstein, Frédéric, Hsieh, Tzung-Chien, Motta, Marialetizia, Radio, Francesca Clementina, Herkert, Johanna C., Rinne, Tuula, Thiffault, Isabelle, Rapp, Michele, Alders, Mariel, Maas, Saskia, Gerard, Bénédicte, Smol, Thomas, Vincent-Delorme, Catherine, Cogné, Benjamin, Isidor, Bertrand, Vincent, Marie, Bachmann-Gagescu, Ruxandra, Rauch, Anita, Joset, Pascal, Ferrero, Giovanni Battista, Ciolfi, Andrea, Husson, Thomas, Guerrot, Anne-Marie, Bacino, Carlos, Macmurdo, Colleen, Thompson, Stephanie S., Rosenfeld, Jill A., Faivre, Laurence, Mau-Them, Frederic Tran, Deb, Wallid, Vignard, Virginie, Agrawal, Pankaj B., Madden, Jill A., Goldenberg, Alice, Lecoquierre, François, Zech, Michael, Prokisch, Holger, Necpál, Ján, Jech, Robert, Winkelmann, Juliane, Koprušáková, Monika Turčanová, Konstantopoulou, Vassiliki, Younce, John R., Shinawi, Marwan, Mighton, Chloe, Fung, Charlotte, Morel, Chantal, Ellis, Jordan Lerner, DiTroia, Stephanie, Barth, Magalie, Bonneau, Dominique, Krapels, Ingrid, Stegmann, Sander, van der Schoot, Vyne, Brunet, Theresa, Bußmann, Cornelia, Mignot, Cyril, Courtin, Thomas, Ravelli, Claudia, Keren, Boris, Ziegler, Alban, Hasadsri, Linda, Pichurin, Pavel N., Klee, Eric W., Grand, Katheryn, Sanchez-Lara, Pedro A., Krüger, Elke, Bézieau, Stéphane, Klinkhammer, Hannah, Krawitz, Peter Michael, Eichler, Evan E., Tartaglia, Marco, Küry, Sébastien, and Wang, Tianyun
- Subjects
Article - Abstract
PURPOSE: De novo variants in CUL3 (Cullin-3 ubiquitin ligase) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here we aimed to collect sporadic cases carrying rare variants in CUL3, describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism. METHODS: Genetic data and detailed clinical records were collected via multi-center collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient-derived T-cells. RESULTS: We assembled a cohort of 35 individuals with heterozygous CUL3 variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 33 have loss-of-function (LoF) and two have missense variants. CUL3 LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin-protein conjugates in vitro . Specifically, we show that cyclin E1 (CCNE1) and 4E-BP1 (EIF4EBP1), two prominent substrates of CUL3, fail to be targeted for proteasomal degradation in patient-derived cells. CONCLUSION: Our study further refines the clinical and mutational spectrum of CUL3 -associated NDDs, expands the spectrum of cullin RING E3 ligase-associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism.
- Published
- 2023
18. Penetrance and Prognosis of MYH7Variant-Associated Cardiomyopathies
- Author
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Jansen, Mark, de Brouwer, Remco, Hassanzada, Fahima, Schoemaker, Angela E., Schmidt, Amand F., Kooijman-Reumerman, Maria D., Bracun, Valentina, Slieker, Martijn G., Dooijes, Dennis, Vermeer, Alexa M.C., Wilde, Arthur A.M., Amin, Ahmad S., Lekanne Deprez, Ronald H., Herkert, Johanna C., Christiaans, Imke, de Boer, Rudolf A., Jongbloed, Jan D.H., van Tintelen, J. Peter, Asselbergs, Folkert W., and Baas, Annette F.
- Abstract
MYH7variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.
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- 2024
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19. Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes.
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Levitin, Maria O, Rawlins, Lettie E, Sanchez-Andrade, Gabriela, Arshad, Osama A, Collins, Stephan C, Sawiak, Stephen J, Iffland, Phillip H, Andersson, Malin H L, Bupp, Caleb, Cambridge, Emma L, Coomber, Eve L, Ellis, Ian, Herkert, Johanna C, Ironfield, Holly, Jory, Logan, Kretz, Perrine F, Kant, Sarina G, Neaverson, Alexandra, Nibbeling, Esther, and Rowley, Christine
- Subjects
INDUCED pluripotent stem cells ,HUMAN stem cells ,CELL morphology ,SIZE of brain ,PATHOLOGICAL physiology - Abstract
KPTN -related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN -related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn
−/− mice display many of the key KPTN -related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants. Molecular and structural analysis of Kptn−/− mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN -related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity. [ABSTRACT FROM AUTHOR]- Published
- 2023
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20. Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome
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Maas, Saskia M., Shaw, Adam C., Bikker, Hennie, Lüdecke, Hermann-Josef, van der Tuin, Karin, Badura-Stronka, Magdalena, Belligni, Elga, Biamino, Elisa, Bonati, Maria Teresa, Carvalho, Daniel R., Cobben, JanMaarten, de Man, Stella A., Den Hollander, Nicolette S., Di Donato, Nataliya, Garavelli, Livia, Grønborg, Sabine, Herkert, Johanna C., Hoogeboom, A. Jeannette M., Jamsheer, Aleksander, Latos-Bielenska, Anna, Maat-Kievit, Anneke, Magnani, Cinzia, Marcelis, Carlo, Mathijssen, Inge B., Nielsen, Maartje, Otten, Ellen, Ousager, Lilian B., Pilch, Jacek, Plomp, Astrid, Poke, Gemma, Poluha, Anna, Posmyk, Renata, Rieubland, Claudine, Silengo, Margharita, Simon, Marleen, Steichen, Elisabeth, Stumpel, Connie, Szakszon, Katalin, Polonkai, Edit, van den Ende, Jenneke, van der Steen, Antony, van Essen, Ton, van Haeringen, Arie, van Hagen, Johanna M., Verheij, Joke B.G.M., Mannens, Marcel M., and Hennekam, Raoul C.
- Published
- 2015
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21. Loss-of-function variants in CUL3 cause a syndromic neurodevelopmental disorder
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Blackburn, Patrick R, Ebstein, Frédéric, Hsieh, Tzung-Chien, Motta, Marialetizia, Radio, Francesca Clementina, Herkert, Johanna C, Rinne, Tuula, Thiffault, Isabelle, Rapp, Michele, Alders, Mariel, Maas, Saskia, Gérard, Bénédicte, Smol, Thomas, Vincent-Delorme, Catherine, Cogné, Benjamin, Isidor, Bertrand, Vincent, Marie, Bachmann-Gagescu, Ruxandra, Rauch, Anita, Joset, Pascal, Ferrero, Giovanni Battista, Ciolfi, Andrea, Husson, Thomas, Guerrot, Anne-Marie, Bacino, Carlos, Macmurdo, Colleen, Thompson, Stephanie S, Rosenfeld, Jill A, Faivre, Laurence, Mau-Them, Frederic Tran, et al, and University of Zurich
- Subjects
Genomic Medicine ,10039 Institute of Medical Genetics ,570 Life sciences ,biology ,610 Medicine & health ,10124 Institute of Molecular Life Sciences ,Genetic Medicine - Published
- 2023
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22. Correction: The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome
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van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Wödl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F. J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W. Y., Chung, Brain H. Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hülya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, López-González, Vanesa, Maas, Saskia, Mancini, Grazia M. S., Marcelis, Carlo, Martinez, Francisco, Maystadt, Isabelle, McGuire, Marianne, McKee, Shane, Mehta, Sarju, Metcalfe, Kay, Milunsky, Jeff, Mizuno, Seiji, Moeschler, John B., Netzer, Christian, Ockeloen, Charlotte W., Oehl-Jaschkowitz, Barbara, Okamoto, Nobuhiko, Olminkhof, Sharon N. M., Orellana, Carmen, Pasquier, Laurent, Pottinger, Caroline, Riehmer, Vera, Robertson, Stephen P., Roifman, Maian, Rooryck, Caroline, Ropers, Fabienne G., Rosello, Monica, Ruivenkamp, Claudia A. L., Sagiroglu, Mahmut S., Sallevelt, Suzanne C. E. H., Calvo, Amparo Sanchis, Simsek-Kiper, Pelin O., Soares, Gabriela, Solaeche, Lucia, Sonmez, Fatma Mujgan, Splitt, Miranda, Steenbeek, Duco, Stegmann, Alexander P. A., Stumpel, Constance T. R. M., Tanabe, Saori, Uctepe, Eyyup, Utine, G. Eda, Veenstra-Knol, Hermine E., Venkateswaran, Sunita, Vilain, Catheline, Vincent-Delorme, Catherine, Vulto-van Silfhout, Anneke T., Wheeler, Patricia, Wilson, Golder N., Wilson, Louise C., Wollnik, Bernd, Kosho, Tomoki, Wieczorek, Dagmar, Eichler, Evan, Pfundt, Rolph, de Vries, Bert B. A., Clayton-Smith, Jill, and Santen, Gijs W. E.
- Published
- 2019
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23. Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort: The Use of Genetic Testing in Risk Stratification
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van der Meulen, Marijke H., primary, Herkert, Johanna C., additional, den Boer, Susanna L., additional, du Marchie Sarvaas, Gideon J., additional, Blom, Nico, additional, ten Harkel, Arend D.J., additional, Breur, Hans M.P.J., additional, Rammeloo, Lukas A.J., additional, Tanke, Ronald, additional, Marcelis, Carlo, additional, van de Laar, Ingrid M.B.H., additional, Verhagen, Judith M.A., additional, Lekanne dit Deprez, Ronald H., additional, Barge-Schaapveld, Daniela Q.C.M., additional, Baas, Annette, additional, Sammani, Arjan, additional, Christiaans, Imke, additional, van Tintelen, J. Peter, additional, and Dalinghaus, Michiel, additional
- Published
- 2022
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24. Mouse and cellular models of KPTN-related disorder implicate mTOR signalling in cognitive and progressive overgrowth phenotypes
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Levitin, Maria O., primary, Rawlins, Lettie E, additional, Sanchez-Andrade, Gabriela, additional, Arshad, Osama A., additional, Collins, Stephan C., additional, Sawiak, Stephen J., additional, Iffland, Phillip H., additional, Andersson, Malin H.L., additional, Bupp, Caleb, additional, Cambridge, Emma L., additional, Coomber, Eve L., additional, Ellis, Ian, additional, Herkert, Johanna C., additional, Ironfield, Holly, additional, Jory, Logan, additional, Kretz, Perrine F., additional, Kant, Sarina G., additional, Neaverson, Alexandra, additional, Nibbeling, Esther, additional, Rowley, Christine, additional, Relton, Emily, additional, Sanderson, Mark, additional, Scott, Ethan M., additional, Stewart, Helen, additional, Shuen, Andrew Y., additional, Schreiber, John, additional, Tuck, Liz, additional, Tonks, James, additional, Terkelsen, Thorkild, additional, van Ravenswaaij-Arts, Conny, additional, Vasudevan, Pradeep, additional, Wenger, Olivia, additional, Wright, Michael, additional, Day, Andrew, additional, Hunter, Adam, additional, Patel, Minal, additional, Lelliott, Christopher J., additional, Crino, Peter B., additional, Yalcin, Binnaz, additional, Crosby, Andrew, additional, Baple, Emma L., additional, Logan, Darren W., additional, Hurles, Matthew E., additional, and Gerety, Sebastian S., additional
- Published
- 2022
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25. Expanding the clinical spectrum of primary coenzyme Q10 deficiency type 6: The first case with cardiomyopathy
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Leeuwen, Lisette, primary, Lubout, Charlotte M. A., additional, Nijenhuis, Hessel P., additional, Meiners, Linda C., additional, Vos, Yvonne J., additional, and Herkert, Johanna C., additional
- Published
- 2022
- Full Text
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26. Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort: The Use of Genetic Testing in Risk Stratification
- Author
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Meulen, M.H. van der, Herkert, Johanna C., Boer, S.L. den, Marchie Sarvaas, G.J. du, Blom, N.A., Harkel, A.D. Ten, Tanke, R.B., Marcelis, C.L.M., Peter van Tintelen, J., Dalinghaus, M., Meulen, M.H. van der, Herkert, Johanna C., Boer, S.L. den, Marchie Sarvaas, G.J. du, Blom, N.A., Harkel, A.D. Ten, Tanke, R.B., Marcelis, C.L.M., Peter van Tintelen, J., and Dalinghaus, M.
- Abstract
Contains fulltext : 284419.pdf (Publisher’s version ) (Open Access)
- Published
- 2022
27. Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort:The Use of Genetic Testing in Risk Stratification
- Author
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van der Meulen, Marijke H., Herkert, Johanna C., den Boer, Susanna L., du Marchie Sarvaas, Gideon J., Blom, Nico A., Ten Harkel, Arend D.J., Breur, Hans M.P.J., Rammeloo, Lukas A.J., Tanke, Ronald B., Marcelis, Carlo, van de Laar, Ingrid M.B.H., Verhagen, Judith M.A., Lekanne Dit Deprez, Ronald H., Barge-Schaapveld, Daniela Q.C.M., Baas, Annette F., Sammani, Arjan, Christiaans, Imke, van Tintelen, J. Peter, Dalinghaus, Michiel, van der Meulen, Marijke H., Herkert, Johanna C., den Boer, Susanna L., du Marchie Sarvaas, Gideon J., Blom, Nico A., Ten Harkel, Arend D.J., Breur, Hans M.P.J., Rammeloo, Lukas A.J., Tanke, Ronald B., Marcelis, Carlo, van de Laar, Ingrid M.B.H., Verhagen, Judith M.A., Lekanne Dit Deprez, Ronald H., Barge-Schaapveld, Daniela Q.C.M., Baas, Annette F., Sammani, Arjan, Christiaans, Imke, van Tintelen, J. Peter, and Dalinghaus, Michiel
- Abstract
BACKGROUND: This study aimed to describe the current practice and results of genetic evaluation in Dutch children with dilated cardiomyopathy and to evaluate genotype-phenotype correlations that may guide prognosis.METHODS: We performed a multicenter observational study in children diagnosed with dilated cardiomyopathy, from 2010 to 2017.RESULTS: One hundred forty-four children were included. Initial diagnostic categories were idiopathic dilated cardiomyopathy in 67 children (47%), myocarditis in 23 (16%), neuromuscular in 7 (5%), familial in 18 (13%), inborn error of metabolism in 4 (3%), malformation syndrome in 2 (1%), and "other" in 23 (16%). Median follow-up time was 2.1 years [IQR 1.0-4.3]. Hundred-seven patients (74%) underwent genetic testing. We found a likely pathogenic or pathogenic variant in 38 children (36%), most often in MYH7 (n = 8). In 1 patient initially diagnosed with myocarditis, a pathogenic LMNA variant was found. During the study, 39 patients (27%) reached study endpoint (SE: all-cause death or heart transplantation). Patients with a likely pathogenic or pathogenic variant were more likely to reach SE compared with those without (hazard ratio 2.8; 95% CI 1.3-5.8, P = 0.007), while transplant-free survival was significantly lower (P = 0.006). Clinical characteristics at diagnosis did not differ between the 2 groups.CONCLUSIONS: Genetic testing is a valuable tool for predicting prognosis in children with dilated cardiomyopathy, with carriers of a likely pathogenic or pathogenic variant having a worse prognosis overall. Genetic testing should be incorporated in clinical work-up of all children with dilated cardiomyopathy regardless of presumed disease pathogenesis.
- Published
- 2022
28. Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort: The Use of Genetic Testing in Risk Stratification
- Author
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Circulatory Health, Cardiologie onderzoek 1, Child Health, Regenerative Medicine and Stem Cells, Genetica Klinische Genetica, Onderzoek Precision medicine, Genetica, van der Meulen, Marijke H, Herkert, Johanna C, den Boer, Susanna L, du Marchie Sarvaas, Gideon J, Blom, Nico, Ten Harkel, Arend D J, Breur, Hans M P J, Rammeloo, Lukas A J, Tanke, Ronald, Marcelis, Carlo, van de Laar, Ingrid M B H, Verhagen, Judith M A, Lekanne Dit Deprez, Ronald H, Barge-Schaapveld, Daniela Q C M, Baas, Annette, Sammani, Arjan, Christiaans, Imke, van Tintelen, J Peter, Dalinghaus, Michiel, Circulatory Health, Cardiologie onderzoek 1, Child Health, Regenerative Medicine and Stem Cells, Genetica Klinische Genetica, Onderzoek Precision medicine, Genetica, van der Meulen, Marijke H, Herkert, Johanna C, den Boer, Susanna L, du Marchie Sarvaas, Gideon J, Blom, Nico, Ten Harkel, Arend D J, Breur, Hans M P J, Rammeloo, Lukas A J, Tanke, Ronald, Marcelis, Carlo, van de Laar, Ingrid M B H, Verhagen, Judith M A, Lekanne Dit Deprez, Ronald H, Barge-Schaapveld, Daniela Q C M, Baas, Annette, Sammani, Arjan, Christiaans, Imke, van Tintelen, J Peter, and Dalinghaus, Michiel
- Published
- 2022
29. Abstract 18198: A Stepwise Approach Including Whole Exome Sequencing Targeting a Gene Panel for Paediatric Dilated Cardiomyopathy, Potentially Yields a Diagnosis in 50% of Patients
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Herkert, Johanna C, Abbott, Kristin M, Birnie, Erwin, Meems-Veldhuis, Martine T, Boven, Ludolf G, Benjamins, Maloes, du Marchie Sarvaas, Gideon J, Barge-Schaapveld, Daniela Q, van Tintelen, J. P, van der Zwaag, Paul A, Vos, Yvonne J, Sinke, Richard J, van den Berg, Maarten P, van Langen, Irene M, and Jongbloed, Jan D
- Published
- 2017
30. Thyroid cancer in a patient with a germline MSH2 mutation. Case report and review of the Lynch syndrome expanding tumour spectrum
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Stulp Rein P, Herkert Johanna C, Karrenbeld Arend, Mol Bart, Vos Yvonne J, and Sijmons Rolf H
- Subjects
Lynch syndrome ,mutations ,MSH2 ,thyroid cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Abstract
Abstract Lynch syndrome (HNPCC) is a dominantly inherited disorder characterized by germline defects in DNA mismatch repair (MMR) genes and the development of a variety of cancers, predominantly colorectal and endometrial. We present a 44-year-old woman who was shown to carry the truncating MSH2 gene mutation that had previously been identified in her family. Recently, she had been diagnosed with an undifferentiated carcinoma of the thyroid and an adenoma of her coecum. Although the thyroid carcinoma was not MSI-high (1 out of 5 microsatellites instable), it did show complete loss of immunohistochemical expression for the MSH2 protein, suggesting that this tumour was not coincidental. Although the risks for some tumour types, including breast cancer, soft tissue sarcoma and prostate cancer, are not significantly increased in Lynch syndrome, MMR deficiency in the presence of a corresponding germline defect has been demonstrated in incidental cases of a growing range of tumour types, which is reviewed in this paper. Interestingly, the MSH2-associated tumour spectrum appears to be wider than that of MLH1 and generally the risk for most extra-colonic cancers appears to be higher for MSH2 than for MLH1 mutation carriers. Together with a previously reported case, our findings show that anaplastic thyroid carcinoma can develop in the setting of Lynch syndrome. Uncommon Lynch syndrome-associated tumour types might be useful in the genetic analysis of a Lynch syndrome suspected family if samples from typical Lynch syndrome tumours are unavailable.
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- 2008
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31. A Study of the Clinical and Radiological Features in a Cohort of 93 Patients with a COL2A1 Mutation Causing Spondyloepiphyseal Dysplasia Congenita or a Related Phenotype
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Terhal, Paulien A., Nievelstein, Rutger Jan A. J., Verver, Eva J. J., Topsakal, Vedat, van Dommelen, Paula, Hoornaert, Kristien, Le Merrer, Martine, Zankl, Andreas, Simon, Marleen E. H., Smithson, Sarah F., Marcelis, Carlo, Kerr, Bronwyn, Clayton-Smith, Jill, Kinning, Esther, Mansour, Sahar, Elmslie, Frances, Goodwin, Linda, van der Hout, Annemarie H., Veenstra-Knol, Hermine E., Herkert, Johanna C., Lund, Allan M., Hennekam, Raoul C. M., Mégarbané, André, Lees, Melissa M., Wilson, Louise C., Male, Alison, Hurst, Jane, Alanay, Yasemin, Annerén, Göran, Betz, Regina C., Bongers, Ernie M. H. F., Cormier-Daire, Valerie, Dieux, Anne, David, Albert, Elting, Mariet W., van den Ende, Jenneke, Green, Andrew, van Hagen, Johanna M., Hertel, Niels Thomas, Holder-Espinasse, Muriel, den Hollander, Nicolette, Homfray, Tessa, Hove, Hanne D., Price, Susan, Raas-Rothschild, Annick, Rohrbach, Marianne, Schroeter, Barbara, Suri, Mohnish, Thompson, Elizabeth M., Tobias, Edward S., Toutain, Annick, Vreeburg, Maaike, Wakeling, Emma, Knoers, Nine V., Coucke, Paul, and Mortier, Geert R.
- Published
- 2015
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32. Screening for germline DND1 mutations in testicular cancer patients
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Sijmons, Rolf H., Vos, Yvonne J., Herkert, Johanna C., Bos, Krista K., Holzik, Martijn F. Lutke, Hoekstra-Weebers, Josette E. H. M., Hofstra, Robert M. W., and Hoekstra, Harald J.
- Published
- 2010
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33. Homozygous damaging SOD2 variant causes lethal neonatal dilated cardiomyopathy
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Almomani, Rowida, Herkert, Johanna C., Posafalvi, Anna, Post, Jan G., Boven, Ludolf G., Zwaag, Paul A. van der, Willems, P.H.G.M., Berg, M.P van den, Rodenburg, R.J., Peter van Tintelen, J., Jongbloed, Jan D.H., Almomani, Rowida, Herkert, Johanna C., Posafalvi, Anna, Post, Jan G., Boven, Ludolf G., Zwaag, Paul A. van der, Willems, P.H.G.M., Berg, M.P van den, Rodenburg, R.J., Peter van Tintelen, J., and Jongbloed, Jan D.H.
- Abstract
Contains fulltext : 214462.pdf (Publisher’s version ) (Closed access)
- Published
- 2020
34. Homozygous damaging SOD2 variant causes lethal neonatal dilated cardiomyopathy
- Author
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Genetica, UMC Utrecht, Genetica Klinische Genetica, Circulatory Health, ZL Neuro-Oncologie Medisch, Pathologie Laboratorium diagnostiek, Pathologie Pathologen staf, Cancer, Almomani, Rowida, Herkert, Johanna C., Posafalvi, Anna, Post, Jan G., Boven, Ludolf G., Van Der Zwaag, Paul A., Willems, Peter H.G.M., Van Veen-Hof, Ingrid H., Verhagen, Judith M.A., Wessels, Marja W., Nikkels, Peter G.J., Wintjes, Liesbeth T., Van Den Berg, Maarten P., Sinke, Richard J., Rodenburg, Richard J., Niezen-Koning, Klary E., Van Tintelen, J. Peter, Jongbloed, Jan D.H., Genetica, UMC Utrecht, Genetica Klinische Genetica, Circulatory Health, ZL Neuro-Oncologie Medisch, Pathologie Laboratorium diagnostiek, Pathologie Pathologen staf, Cancer, Almomani, Rowida, Herkert, Johanna C., Posafalvi, Anna, Post, Jan G., Boven, Ludolf G., Van Der Zwaag, Paul A., Willems, Peter H.G.M., Van Veen-Hof, Ingrid H., Verhagen, Judith M.A., Wessels, Marja W., Nikkels, Peter G.J., Wintjes, Liesbeth T., Van Den Berg, Maarten P., Sinke, Richard J., Rodenburg, Richard J., Niezen-Koning, Klary E., Van Tintelen, J. Peter, and Jongbloed, Jan D.H.
- Published
- 2020
35. Lifelines COVID-19 cohort: investigating COVID-19 infection and its health and societal impacts in a Dutch population-based cohort
- Author
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Mc Intyre, Katherine, primary, Lanting, Pauline, additional, Deelen, Patrick, additional, Wiersma, Henry H, additional, Vonk, Judith M, additional, Ori, Anil P S, additional, Jankipersadsing, Soesma A, additional, Warmerdam, Robert, additional, van Blokland, Irene, additional, Boulogne, Floranne, additional, Dijkema, Marjolein X L, additional, Herkert, Johanna C, additional, Claringbould, Annique, additional, Bakker, Olivier, additional, Lopera Maya, Esteban A, additional, Bültmann, Ute, additional, Zhernakova, Alexandra, additional, Reijneveld, Sijmen A, additional, Zijlstra, Elianne, additional, Swertz, Morris A, additional, Brouwer, Sandra, additional, van Ooijen, Raun, additional, Angelini, Viola, additional, Dekker, Louise H, additional, Sijtsma, Anna, additional, Scherjon, Sicco A, additional, Wijmenga, Cisca, additional, Dekens, Jackie A M, additional, Mierau, Jochen, additional, Boezen, H Marike, additional, and Franke, Lude, additional
- Published
- 2021
- Full Text
- View/download PDF
36. Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy
- Author
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Lahrouchi, Najim, primary, Postma, Alex V., additional, Salazar, Christian M., additional, De Laughter, Daniel M., additional, Tjong, Fleur, additional, Piherová, Lenka, additional, Bowling, Forrest Z., additional, Zimmerman, Dominic, additional, Lodder, Elisabeth M., additional, Ta-Shma, Asaf, additional, Perles, Zeev, additional, Beekman, Leander, additional, Ilgun, Aho, additional, Gunst, Quinn, additional, Hababa, Mariam, additional, Škorić-Milosavljević, Doris, additional, Stránecký, Viktor, additional, Tomek, Viktor, additional, de Knijff, Peter, additional, de Leeuw, Rick, additional, Robinson, Jamille Y., additional, Burn, Sabrina C., additional, Mustafa, Hiba, additional, Ambrose, Matthew, additional, Moss, Timothy, additional, Jacober, Jennifer, additional, Niyazov, Dmitriy M., additional, Wolf, Barry, additional, Kim, Katherine H., additional, Cherny, Sara, additional, Rousounides, Andreas, additional, Aristidou-Kallika, Aphrodite, additional, Tanteles, George, additional, Ange-Line, Bruel, additional, Denommé-Pichon, Anne-Sophie, additional, Francannet, Christine, additional, Ortiz, Damara, additional, Haak, Monique C., additional, Harkel, Arend D. J. Ten, additional, Manten, Gwendolyn T.R., additional, Dutman, Annemiek C., additional, Bouman, Katelijne, additional, Magliozzi, Monia, additional, Radio, Francesca Clementina, additional, Santen, Gijs W.E., additional, Herkert, Johanna C., additional, Brown, H. Alex, additional, Elpeleg, Orly, additional, van den Hoff, Maurice J.B., additional, Mulder, Barbara, additional, Airola, Michael V., additional, Kmoch, Stanislav, additional, Barnett, Joey V., additional, Clur, Sally-Ann, additional, Frohman, Michael A., additional, and Bezzina, Connie R., additional
- Published
- 2021
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- View/download PDF
37. Calibration of Multiple In Silico Tools for Predicting Pathogenicity of Mismatch Repair Gene Missense Substitutions
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Thompson, Bryony A., Greenblatt, Marc S., Vallee, Maxime P., Herkert, Johanna C., Tessereau, Chloe, Young, Erin L., Adzhubey, Ivan A., Li, Biao, Bell, Russell, Feng, Bingjian, Mooney, Sean D., Radivojac, Predrag, Sunyaev, Shamil R., Frebourg, Thierry, Hofstra, Robert M.W., Sijmons, Rolf H., Boucher, Ken, Thomas, Alun, Goldgar, David E., Spurdle, Amanda B., and Tavtigian, Sean V.
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- 2013
- Full Text
- View/download PDF
38. Expanding the clinical and genetic spectrum of ALPK3 variants: Phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants
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Herkert, Johanna C., primary, Verhagen, Judith M.A., additional, Yotti, Raquel, additional, Haghighi, Alireza, additional, Phelan, Dean G., additional, James, Paul A., additional, Brown, Natasha J., additional, Stutterd, Chloe, additional, Macciocca, Ivan, additional, Leong, Kai'En, additional, Bulthuis, Marian L.C., additional, van Bever, Yolande, additional, van Slegtenhorst, Marjon A., additional, Boven, Ludolf G., additional, Roberts, Amy E., additional, Agarwal, Radhika, additional, Seidman, Jonathan, additional, Lakdawala, Neal K., additional, Fernández-Avilés, Francisco, additional, Burke, Michael A., additional, Pierpont, Mary Ella., additional, Braunlin, Elizabeth, additional, Ḉağlayan, Ahmet Okay, additional, Barge-Schaapveld, Daniela Q.C.M., additional, Birnie, Erwin, additional, van Osch-Gevers, Lennie, additional, van Langen, Irene M., additional, Jongbloed, Jan D.H., additional, Lockhart, Paul J., additional, Amor, David J., additional, Seidman, Christine E., additional, and van de Laar, Ingrid M.B.H., additional
- Published
- 2020
- Full Text
- View/download PDF
39. The Lifelines COVID-19 Cohort: a questionnaire-based study to investigate COVID-19 infection and its health and societal impacts in a Dutch population-based cohort
- Author
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Intyre, Kate Mc, primary, Lanting, Pauline, additional, Deelen, Patrick, additional, Wiersma, Henry, additional, Vonk, Judith M., additional, Ori, Anil P.S., additional, Jankipersadsing, Soesma A., additional, Warmerdam, Robert, additional, van Blokland, Irene, additional, Boulogne, Floranne, additional, Dijkema, Marjolein X.L., additional, Herkert, Johanna C., additional, Claringbould, Annique, additional, Bakker, Olivier, additional, Lopera Maya, Esteban A., additional, Bültmann, Ute, additional, Zhernakova, Alexandra, additional, Reijneveld, Sijmen A., additional, Zijlstra, Elianne, additional, Swertz, Morris, additional, Brouwer, Sandra, additional, van Ooijen, R., additional, Angelini, Viola, additional, Dekker, Louise, additional, Sijtsma, Anna, additional, Scherjon, Sicco A., additional, Dekens, Jackie, additional, Mierau, Jochen O., additional, Boezen, H. Marike, additional, and Franke, Lude, additional
- Published
- 2020
- Full Text
- View/download PDF
40. ZMYND11 ‐related syndromic intellectual disability: 16 patients delineating and expanding the phenotypic spectrum
- Author
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Yates, Thabo M., primary, Drucker, Morgan, additional, Barnicoat, Angela, additional, Low, Karen, additional, Gerkes, Erica H., additional, Fry, Andrew E., additional, Parker, Michael J., additional, O'Driscoll, Mary, additional, Charles, Perrine, additional, Cox, Helen, additional, Marey, Isabelle, additional, Keren, Boris, additional, Rinne, Tuula, additional, McEntagart, Meriel, additional, Ramachandran, Vijaya, additional, Drury, Suzanne, additional, Vansenne, Fleur, additional, Sival, Deborah A., additional, Herkert, Johanna C., additional, Callewaert, Bert, additional, Tan, Wen‐Hann, additional, and Balasubramanian, Meena, additional
- Published
- 2020
- Full Text
- View/download PDF
41. Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy
- Author
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Verhagen, Judith M.A., van den Born, Myrthe, van der Linde, Herma C., G J Nikkels, Peter, Verdijk, Rob M., Kivlen, Maryann H., van Unen, Leontine M.A., Baas, Annette F., Ter Heide, Henriette, van Osch-Gevers, Lennie, Hoogeveen-Westerveld, Marianne, Herkert, Johanna C., Bertoli-Avella, Aida M., van Slegtenhorst, Marjon A., Wessels, Marja W., Verheijen, Frans W., Hassel, David, Hofstra, Robert M.W., Hegde, Ramanujan S., van Hasselt, Peter M., van Ham, Tjakko J., van de Laar, Ingrid M.B.H., Verhagen, Judith M.A., van den Born, Myrthe, van der Linde, Herma C., G J Nikkels, Peter, Verdijk, Rob M., Kivlen, Maryann H., van Unen, Leontine M.A., Baas, Annette F., Ter Heide, Henriette, van Osch-Gevers, Lennie, Hoogeveen-Westerveld, Marianne, Herkert, Johanna C., Bertoli-Avella, Aida M., van Slegtenhorst, Marjon A., Wessels, Marja W., Verheijen, Frans W., Hassel, David, Hofstra, Robert M.W., Hegde, Ramanujan S., van Hasselt, Peter M., van Ham, Tjakko J., and van de Laar, Ingrid M.B.H.
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- 2019
42. Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy
- Author
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UMC Utrecht, Pathologie Pathologen staf, Cancer, Genetica Klinische Genetica, Circulatory Health, Cardiologie patientenzorg, Child Health, Cluster C, Metabole ziekten patientenzorg, Verhagen, Judith M.A., van den Born, Myrthe, van der Linde, Herma C., G J Nikkels, Peter, Verdijk, Rob M., Kivlen, Maryann H., van Unen, Leontine M.A., Baas, Annette F., Ter Heide, Henriette, van Osch-Gevers, Lennie, Hoogeveen-Westerveld, Marianne, Herkert, Johanna C., Bertoli-Avella, Aida M., van Slegtenhorst, Marjon A., Wessels, Marja W., Verheijen, Frans W., Hassel, David, Hofstra, Robert M.W., Hegde, Ramanujan S., van Hasselt, Peter M., van Ham, Tjakko J., van de Laar, Ingrid M.B.H., UMC Utrecht, Pathologie Pathologen staf, Cancer, Genetica Klinische Genetica, Circulatory Health, Cardiologie patientenzorg, Child Health, Cluster C, Metabole ziekten patientenzorg, Verhagen, Judith M.A., van den Born, Myrthe, van der Linde, Herma C., G J Nikkels, Peter, Verdijk, Rob M., Kivlen, Maryann H., van Unen, Leontine M.A., Baas, Annette F., Ter Heide, Henriette, van Osch-Gevers, Lennie, Hoogeveen-Westerveld, Marianne, Herkert, Johanna C., Bertoli-Avella, Aida M., van Slegtenhorst, Marjon A., Wessels, Marja W., Verheijen, Frans W., Hassel, David, Hofstra, Robert M.W., Hegde, Ramanujan S., van Hasselt, Peter M., van Ham, Tjakko J., and van de Laar, Ingrid M.B.H.
- Published
- 2019
43. The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome
- Author
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Karabey, Hülya Kayserili (ORCID 0000-0003-0376-499X & YÖK ID 7945), van der Sluijs, Pleuntje J.; Jansen, Sandra; Vergano, Samantha A.; Adachi-Fukuda, Miho; Alanay, Yasemin; AlKindy, Adila; Baban, Anwar; Bayat, Allan; Beck-Woedl, Stefanie; Berry, Katherine; Bijlsma, Emilia K.; Bok, Levinus A.; Brouwer, Alwin F. J.; van der Burgt, Ineke; Campeau, Philippe M.; Canham, Natalie; Chrzanowska, Krystyna; Chu, Yoyo W. Y.; Chung, Brain H. Y.; Dahan, Karin; De Rademaeker, Marjan; Destree, Anne; Dudding-Byth, Tracy; Earl, Rachel; Elçioğlu, Nursel; Elias, Ellen R.; Fagerberg, Christina; Gardham, Alice; Gener, Blanca; Gerkes, Erica H.; Grasshoff, Ute; van Haeringen, Arie; Heitink, Karin R.; Herkert, Johanna C.; den Hollander, Nicolette S.; Horn, Denise; Hunt, David; Kant, Sarina G.; Kato, Mitsuhiro; Kersseboom, Rogier; Kılıç, Esra; Krajewska-Walasek, Malgorzata; Lammers, Kylin; Laulund, Lone W.; Lederer, Damien; Lees, Melissa; Lopez-Gonzalez, Vanesa; Maas, Saskia; Mancini, Grazia M. S.; Marcelis, Carlo; Martinez, Francisco; Maystadt, Isabelle; McGuire, Marianne; McKee, Shane; Mehta, Sarju; Metcalfe, Kay; Milunsky, Jeff; Mizuno, Seiji; Moeschler, John B.; Netzer, Christian; Ockeloen, Charlotte W.; Oehl-Jaschkowitz, Barbara; Okamoto, Nobuhiko; Olminkhof, Sharon N. M.; Orellana, Carmen; Pasquier, Laurent; Pottinger, Caroline; Riehmer, Vera; Robertson, Stephen P.; Roifman, Maian; Rooryck, Caroline; Ropers, Fabienne G.; Rosello, Monica; Ruivenkamp, Claudia A. L.; Sağıroğlu, Mahmut S.; Sallevelt, Suzanne C. E. H.; Sanchis Calvo, Amparo; Şimşek-Kiper, Pelin O.; Soares, Gabriela; Solaeche, Lucia; Sönmez, Fatma Müjgan; Splitt, Miranda; Steenbeek, Duco; Stegmann, Alexander P. A.; Stumpel, Constance T. R. M.; Tanabe, Saori; Üçtepe, Eyyüp; Utine, G. Eda; Veenstra-Knol, Hermine E.; Venkateswaran, Sunita; Vilain, Catheline; Vincent-Delorme, Catherine; Vulto-van Silfhout, Anneke T.; Wheeler, Patricia; Wilson, Golder N.; Wilson, Louise C.; Wollnik, Bernd; Kosho, Tomoki; Wieczorek, Dagmar; Eichler, Evan; Pfundt, Rolph; de Vries, Bert B. A.; Clayton-Smith, Jill; S, School of Medicine, Department of Medical Genetics, Karabey, Hülya Kayserili (ORCID 0000-0003-0376-499X & YÖK ID 7945), van der Sluijs, Pleuntje J.; Jansen, Sandra; Vergano, Samantha A.; Adachi-Fukuda, Miho; Alanay, Yasemin; AlKindy, Adila; Baban, Anwar; Bayat, Allan; Beck-Woedl, Stefanie; Berry, Katherine; Bijlsma, Emilia K.; Bok, Levinus A.; Brouwer, Alwin F. J.; van der Burgt, Ineke; Campeau, Philippe M.; Canham, Natalie; Chrzanowska, Krystyna; Chu, Yoyo W. Y.; Chung, Brain H. Y.; Dahan, Karin; De Rademaeker, Marjan; Destree, Anne; Dudding-Byth, Tracy; Earl, Rachel; Elçioğlu, Nursel; Elias, Ellen R.; Fagerberg, Christina; Gardham, Alice; Gener, Blanca; Gerkes, Erica H.; Grasshoff, Ute; van Haeringen, Arie; Heitink, Karin R.; Herkert, Johanna C.; den Hollander, Nicolette S.; Horn, Denise; Hunt, David; Kant, Sarina G.; Kato, Mitsuhiro; Kersseboom, Rogier; Kılıç, Esra; Krajewska-Walasek, Malgorzata; Lammers, Kylin; Laulund, Lone W.; Lederer, Damien; Lees, Melissa; Lopez-Gonzalez, Vanesa; Maas, Saskia; Mancini, Grazia M. S.; Marcelis, Carlo; Martinez, Francisco; Maystadt, Isabelle; McGuire, Marianne; McKee, Shane; Mehta, Sarju; Metcalfe, Kay; Milunsky, Jeff; Mizuno, Seiji; Moeschler, John B.; Netzer, Christian; Ockeloen, Charlotte W.; Oehl-Jaschkowitz, Barbara; Okamoto, Nobuhiko; Olminkhof, Sharon N. M.; Orellana, Carmen; Pasquier, Laurent; Pottinger, Caroline; Riehmer, Vera; Robertson, Stephen P.; Roifman, Maian; Rooryck, Caroline; Ropers, Fabienne G.; Rosello, Monica; Ruivenkamp, Claudia A. L.; Sağıroğlu, Mahmut S.; Sallevelt, Suzanne C. E. H.; Sanchis Calvo, Amparo; Şimşek-Kiper, Pelin O.; Soares, Gabriela; Solaeche, Lucia; Sönmez, Fatma Müjgan; Splitt, Miranda; Steenbeek, Duco; Stegmann, Alexander P. A.; Stumpel, Constance T. R. M.; Tanabe, Saori; Üçtepe, Eyyüp; Utine, G. Eda; Veenstra-Knol, Hermine E.; Venkateswaran, Sunita; Vilain, Catheline; Vincent-Delorme, Catherine; Vulto-van Silfhout, Anneke T.; Wheeler, Patricia; Wilson, Golder N.; Wilson, Louise C.; Wollnik, Bernd; Kosho, Tomoki; Wieczorek, Dagmar; Eichler, Evan; Pfundt, Rolph; de Vries, Bert B. A.; Clayton-Smith, Jill; S, School of Medicine, and Department of Medical Genetics
- Abstract
Purpose: pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: there are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features., Netherlands Organisation for Health Research and Development
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- 2019
44. The ARID1B spectrum in 143 patients:from nonsyndromic intellectual disability to Coffin–Siris syndrome
- Author
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van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Wödl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F.J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W.Y., Chung, Brain H.Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hülya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, López-González, Vanesa, Maas, Saskia, Mancini, Grazia M.S., van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Wödl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F.J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W.Y., Chung, Brain H.Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hülya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, López-González, Vanesa, Maas, Saskia, and Mancini, Grazia M.S.
- Abstract
Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features.
- Published
- 2019
45. Correction:The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome (Genetics in Medicine, (2019), 21, 6, (1295-1307), 10.1038/s41436-018-0330-z)
- Author
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van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Wödl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F.J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W.Y., Chung, Brain H.Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hülya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, López-González, Vanesa, Maas, Saskia, Mancini, Grazia M.S., van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Wödl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F.J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W.Y., Chung, Brain H.Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hülya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, López-González, Vanesa, Maas, Saskia, and Mancini, Grazia M.S.
- Abstract
The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article.
- Published
- 2019
46. Using symptom-based case predictions to identify host genetic factors that contribute to COVID-19 susceptibility.
- Author
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van Blokland, Irene V., Lanting, Pauline, Ori, Anil P. S., Vonk, Judith M., Warmerdam, Robert C. A., Herkert, Johanna C., Boulogne, Floranne, Claringbould, Annique, Lopera-Maya, Esteban A., Bartels, Meike, Hottenga, Jouke-Jan, Ganna, Andrea, Karjalainen, Juha, Hayward, Caroline, Fawns-Ritchie, Chloe, Campbell, Archie, Porteous, David, Cirulli, Elizabeth T., Schiabor Barrett, Kelly M., and Riffle, Stephen
- Subjects
COVID-19 ,COVID-19 pandemic ,VIRUS diseases ,GENETIC variation ,SARS-CoV-2 - Abstract
Epidemiological and genetic studies on COVID-19 are currently hindered by inconsistent and limited testing policies to confirm SARS-CoV-2 infection. Recently, it was shown that it is possible to predict COVID-19 cases using cross-sectional self-reported disease-related symptoms. Here, we demonstrate that this COVID-19 prediction model has reasonable and consistent performance across multiple independent cohorts and that our attempt to improve upon this model did not result in improved predictions. Using the existing COVID-19 prediction model, we then conducted a GWAS on the predicted phenotype using a total of 1,865 predicted cases and 29,174 controls. While we did not find any common, large-effect variants that reached genome-wide significance, we do observe suggestive genetic associations at two SNPs (rs11844522, p = 1.9x10-7; rs5798227, p = 2.2x10-7). Explorative analyses furthermore suggest that genetic variants associated with other viral infectious diseases do not overlap with COVID-19 susceptibility and that severity of COVID-19 may have a different genetic architecture compared to COVID-19 susceptibility. This study represents a first effort that uses a symptom-based predicted phenotype as a proxy for COVID-19 in our pursuit of understanding the genetic susceptibility of the disease. We conclude that the inclusion of symptom-based predicted cases could be a useful strategy in a scenario of limited testing, either during the current COVID-19 pandemic or any future viral outbreak. [ABSTRACT FROM AUTHOR]
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- 2021
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- View/download PDF
47. Homozygous damaging SOD2 variant causes lethal neonatal dilated cardiomyopathy
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Almomani, Rowida, primary, Herkert, Johanna C, additional, Posafalvi, Anna, additional, Post, Jan G, additional, Boven, Ludolf G, additional, van der Zwaag, Paul A, additional, Willems, Peter H G M, additional, van Veen-Hof, Ingrid H, additional, Verhagen, Judith M A, additional, Wessels, Marja W, additional, Nikkels, Peter G J, additional, Wintjes, Liesbeth T, additional, van den Berg, Maarten P, additional, Sinke, Richard J, additional, Rodenburg, Richard J, additional, Niezen-Koning, Klary E, additional, van Tintelen, J Peter, additional, and Jongbloed, Jan D H, additional
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- 2019
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48. Biallelic Variants in ASNA1 , Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy
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Verhagen, Judith M.A., primary, van den Born, Myrthe, additional, van der Linde, Herma C., additional, G.J. Nikkels, Peter, additional, Verdijk, Rob M., additional, Kivlen, Maryann H., additional, van Unen, Leontine M.A., additional, Baas, Annette F., additional, ter Heide, Henriette, additional, van Osch-Gevers, Lennie, additional, Hoogeveen-Westerveld, Marianne, additional, Herkert, Johanna C., additional, Bertoli-Avella, Aida M., additional, van Slegtenhorst, Marjon A., additional, Wessels, Marja W., additional, Verheijen, Frans W., additional, Hassel, David, additional, Hofstra, Robert M.W., additional, Hegde, Ramanujan S., additional, van Hasselt, Peter M., additional, van Ham, Tjakko J., additional, and van de Laar, Ingrid M.B.H., additional
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- 2019
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49. Improving the diagnostic yield of exome- sequencing by predicting gene–phenotype associations using large-scale gene expression analysis
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Deelen, Patrick, primary, van Dam, Sipko, additional, Herkert, Johanna C., additional, Karjalainen, Juha M., additional, Brugge, Harm, additional, Abbott, Kristin M., additional, van Diemen, Cleo C., additional, van der Zwaag, Paul A., additional, Gerkes, Erica H., additional, Zonneveld-Huijssoon, Evelien, additional, Boer-Bergsma, Jelkje J., additional, Folkertsma, Pytrik, additional, Gillett, Tessa, additional, van der Velde, K. Joeri, additional, Kanninga, Roan, additional, van den Akker, Peter C., additional, Jan, Sabrina Z., additional, Hoorntje, Edgar T., additional, te Rijdt, Wouter P., additional, Vos, Yvonne J., additional, Jongbloed, Jan D. H., additional, van Ravenswaaij-Arts, Conny M. A., additional, Sinke, Richard, additional, Sikkema-Raddatz, Birgit, additional, Kerstjens-Frederikse, Wilhelmina S., additional, Swertz, Morris A., additional, and Franke, Lude, additional
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- 2019
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50. A stepwise approach including whole exome sequencing targeting a gene panel for paediatric dilated cardiomyopathy, potentially yields a diagnosis in 50% of patients
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Herkert, Johanna C., Abbott, Kristin M., Birnie, Erwin, Meems-Veldhuis, Martine T., Boven, Ludolf G., Benjamins, Maloes, Sarvaas, Gideon J. du Marchie, Barge-Schaapveld, Daniela Q., van Tintelen, J. P., van der Zwaag, Paul A., Vos, Yvonne J., Sinke, Richard J., van den Berg, Maarten P., van Langen, Irene M., Jongbloed, Jan D., Cardiovascular Centre (CVC), Reproductive Origins of Adult Health and Disease (ROAHD), and Health Psychology Research (HPR)
- Subjects
GM1 gangliosidosis ,endogenous compound ,diagnosis ,phenotype ,centronuclear myopathy ,whole exome sequencing ,incidental finding ,male ,prevention ,single nucleotide polymorphism ,congestive cardiomyopathy ,sodium channel Nav1.5 ,heterozygosity ,human ,microcephaly ,ontology ,filtration ,child ,troponin T ,gene deletion ,adult ,copy number variation ,cohort analysis ,major clinical study ,female ,young adult ,diagnostic value ,homozygosity ,mutation ,myosin heavy chain beta - Abstract
Introduction: Dilated cardiomyopathy (DCM) is a progressive disease of heart muscle with an incidence of approximately 0.57 per 100,000 children in the US. The spectrum and frequency of mutations in known DCM genes differ among adults, children, and infants. Aim: To evaluate the diagnostic yield of genome-wide copy number variation (CNV) analysis and trio Whole Exome Sequencing (WES) with targeted analysis of genes implicated in paediatric DCM. Methods: We identified 95 cases (from 85 families) diagnosed with DCM before 18 years of age. Thirteen families with a genetic diagnosis that was previously established by other sequencing techniques were excluded, and 41 families for other reasons. In 31 carefully phenotyped probands CNV-analysis (SNP-array) and trio-WES were performed. Human Phenotype Ontology (HPO)-terms were used for data filtering. Results: A (likely) genetic diagnosis could be made in 14/31 families (45.2%). (Likely) pathogenic heterozygous variants were identified in TNNT2, SCN5A, TTN, MYH7 (4), MYL2 (2) and TPM1, and homozygous variants in SPEG (centronuclear myopathy) and GLB1 (GM1-gangliosidosis) using WES, as well as an 1p36.33p36.32 and an 10q25.2 deletion, using SNP-array. Compound heterozygous mutations in CEP135 (primary microcephaly) were identified in a child with syndromic DCM. Five patients carried autosomal recessive disease mutations that did not explain their phenotypes. Conclusions: WES and CNV-analysis yielded diagnoses for 45% of our cohort. In 8/10 families 'solved' by WES a causal variant in a well-known DCM gene was identified. When CNV-analysis and WES would have been applied as primary tests to all patients, the potential yield could increase to approximately 51%. Combining CNV-analysis with trio-based WES, filtering for variants in a virtual, and flexible gene panel based on patient-specific HPO-terms, represent a comprehensive, personalized, cost-and time-efficient strategy to establish a diagnosis within the genetically highly heterogeneous paediatric DCM cohort. The latter technique provides the ability to stepwise analysis of a subset of genomic data, thereby minimizing the number of variants of unknown significance and preventing incidental findings in a proportion of patients.
- Published
- 2017
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