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1. Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes

Author

Rots, Dmitrijs, Choufani, Sanaa, Faundes, Victor, Dingemans, Alexander J.M., Joss, Shelagh, Foulds, Nicola, Jones, Elizabeth A., Stewart, Sarah, Vasudevan, Pradeep, Dabir, Tabib, Park, Soo-Mi, Jewell, Rosalyn, Brown, Natasha, Pais, Lynn, Jacquemont, Sébastien, Jizi, Khadijé, Ravenswaaij-Arts, Conny M.A. van, Kroes, Hester Y., Stumpel, Constance T.R. M., Ockeloen, Charlotte W., Diets, Illja J., Nizon, Mathilde, Vincent, Marie, Cogné, Benjamin, Besnard, Thomas, Kambouris, Marios, Anderson, Emily, Zackai, Elaine H., McDougall, Carey, Donoghue, Sarah, O'Donnell-Luria, Anne, Valivullah, Zaheer, O'Leary, Melanie, Srivastava, Siddharth, Byers, Heather, Leslie, Nancy, Mazzola, Sarah, Tiller, George E., Vera, Moin, Shen, Joseph J., Boles, Richard, Jain, Vani, Brischoux-Boucher, Elise, Kinning, Esther, Simpson, Brittany N., Giltay, Jacques C., Harris, Jacqueline, Keren, Boris, Guimier, Anne, Marijon, Pierre, Vries, Bert B.A. de, Motter, Constance S., Mendelsohn, Bryce A., Coffino, Samantha, Gerkes, Erica H., Afenjar, Alexandra, Visconti, Paola, Bacchelli, Elena, Maestrini, Elena, Delahaye-Duriez, Andree, Gooch, Catherine, Hendriks, Yvonne, Adams, Hieab, Thauvin-Robinet, Christel, Josephi-Taylor, Sarah, Bertoli, Marta, Parker, Michael J., Rutten, Julie W., Caluseriu, Oana, Vernon, Hilary J., Kaziyev, Jonah, Zhu, Jia, Kremen, Jessica, Frazier, Zoe, Osika, Hailey, Breault, David, Nair, Sreelata, Lewis, Suzanne M.E., Ceroni, Fabiola, Viggiano, Marta, Posar, Annio, Brittain, Helen, Giovanna, Traficante, Giulia, Gori, Quteineh, Lina, Ha-Vinh Leuchter, Russia, Zonneveld-Huijssoon, Evelien, Mellado, Cecilia, Marey, Isabelle, Coudert, Alicia, Aracena Alvarez, Mariana Inés, Kennis, Milou G.P., Bouman, Arianne, Roifman, Maian, Amorós Rodríguez, María Inmaculada, Ortigoza-Escobar, Juan Dario, Vernimmen, Vivian, Sinnema, Margje, Pfundt, Rolph, Brunner, Han G., Vissers, Lisenka E.L.M., Kleefstra, Tjitske, Weksberg, Rosanna, and Banka, Siddharth

Published
2024
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2. Menke-Hennekam syndrome; delineation of domain-specific subtypes with distinct clinical and DNA methylation profiles

Author

Angius, Andrea, Baker, Janice A., Bedoukian, Emma, Bhambhani, Vikas, Bodamer, Olaf, O’Brien, Alan, Clayton-Smith, Jill, Crisponi, Laura, Cueto González, Anna María, the DDD study, Devriendt, Koenraad, Garrido, Elena Dominguez, Ehmke, Nadja, van Eerde, Albertien, van den Elzen, Annette P.M., Faivre, Laurence, Fisher, Laura, Flores-Daboub, Josue A., Foster, Alison, Friedman, Jennifer, Gabau, Elisabeth, Galazzi, Elena, García-Miñaúr, Sixto, Garavelli, Livia, Gardeitchik, Thatjana, Gerkes, Erica H., van Gils, Julien, Giltay, Jacques C., Garcia, Aixa Gonzalez, Heimdal, Ketil Riddervold, Horn, Denise, Houge, Gunnar, Hufnagel, Sophia B., Ilencikova, Denisa, Julia, Sophie, Kant, Sarina G., Kinning, Esther, Klee, Eric W., Kois, Chelsea, Kovačević, Maja, Lachmeijer, A.M.A. (Guus), Lanpher, Brendan, Lebrun, Marine, Leon, Eyby, Lichty, Angie Ward, Lin, Ruth, Llano-Rivas, Isabel, Lynch, Sally Ann, Maas, Saskia M., Maitz, Silvia B., McKee, Shane, Melis, Daniela, Merati, Elisabetta, Merla, Giuseppe, Newbury-Ecob, Ruth, Nizon, Mathilde, Park, Soo-Mi, Patterson, Jennifer, Petit, Florence, Peeters, Hilde, Persani, Luca, Persico, Ivana, Pes, Valentina, Pollazzon, Marzia, Potjer, Thomas, Potocki, Lorraine, Pottinger, Carrie, Prasad, Chitra, Prijoles, Eloise J., Ragge, Nicola K., Rake, Jan Peter, van Ravenswaaij-Arts, Conny M.A., Rea, Gillian, Ruivenkamp, Claudia, Rutz, Audrey, Saitta, Sulagna C., Russo, Rossana Sanchez, Santen, Gijs W.E., Schaefer, Elise, Shashi, Vandana, Schultz-Rogers, Laura, Sluga, Andrea, Sotgiu, Stefano, Steichen-Gersdorf, Elisabeth, Sullivan, Jennifer A., Sun, Yu, Suri, Mohnish, Tartaglia, Marco, Tedder, Matt, Terhal, Paulien, Tully, Ian, Verbeek, Nienke, Wenzel, Maren, White, Susan M., Xiao, Bing, Haghshenas, Sadegheh, Bout, Hidde J., Schijns, Josephine M., Levy, Michael A., Kerkhof, Jennifer, Bhai, Pratibha, McConkey, Haley, Jenkins, Zandra A., Williams, Ella M., Halliday, Benjamin J., Huisman, Sylvia A., Lauffer, Peter, de Waard, Vivian, Witteveen, Laura, Banka, Siddharth, Brady, Angela F., Hurst, Anna C.E., Kaiser, Frank J., Lacombe, Didier, Martinez-Monseny, Antonio F., Fergelot, Patricia, Monteiro, Fabíola P., Parenti, Ilaria, Santos-Simarro, Fernando, Simpson, Brittany N., Alders, Mariëlle, Robertson, Stephen P., Sadikovic, Bekim, and Menke, Leonie A.

Published
2024
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3. Identification of DNA methylation episignature for the intellectual developmental disorder, autosomal dominant 21 syndrome, caused by variants in the CTCF gene

Author

Karimi, Karim, Mol, Merel O., Haghshenas, Sadegheh, Relator, Raissa, Levy, Michael A., Kerkhof, Jennifer, McConkey, Haley, Brooks, Alice, Zonneveld-Huijssoon, Evelien, Gerkes, Erica H., Tedder, Matthew L., Vissers, Lisenka, Salzano, Emanuela, Piccione, Maria, Asaftei, Sebastian Dorin, Carli, Diana, Mussa, Alessandro, Shukarova-Angelovska, Elena, Trajkova, Slavica, Brusco, Alfredo, Merla, Giuseppe, Alders, Marielle M., Bouman, Arjan, and Sadikovic, Bekim

Published
2024
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4. Widening of the genetic and clinical spectrum of Lamb–Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency

Author

Zawerton, Ash, Mignot, Cyril, Sigafoos, Ashley, Blackburn, Patrick R, Haseeb, Abdul, McWalter, Kirsty, Ichikawa, Shoji, Nava, Caroline, Keren, Boris, Charles, Perrine, Marey, Isabelle, Tabet, Anne-Claude, Levy, Jonathan, Perrin, Laurence, Hartmann, Andreas, Lesca, Gaetan, Schluth-Bolard, Caroline, Monin, Pauline, Dupuis-Girod, Sophie, Guillen Sacoto, Maria J, Schnur, Rhonda E, Zhu, Zehua, Poisson, Alice, El Chehadeh, Salima, Alembik, Yves, Bruel, Ange-Line, Lehalle, Daphné, Nambot, Sophie, Moutton, Sébastien, Odent, Sylvie, Jaillard, Sylvie, Dubourg, Christèle, Hilhorst-Hofstee, Yvonne, Barbaro-Dieber, Tina, Ortega, Lucia, Bhoj, Elizabeth J, Masser-Frye, Diane, Bird, Lynne M, Lindstrom, Kristin, Ramsey, Keri M, Narayanan, Vinodh, Fassi, Emily, Willing, Marcia, Cole, Trevor, Salter, Claire G, Akilapa, Rhoda, Vandersteen, Anthony, Canham, Natalie, Rump, Patrick, Gerkes, Erica H, Klein Wassink-Ruiter, Jolien S, Bijlsma, Emilia, Hoffer, Mariëtte JV, Vargas, Marcelo, Wojcik, Antonina, Cherik, Florian, Francannet, Christine, Rosenfeld, Jill A, Machol, Keren, Scott, Daryl A, Bacino, Carlos A, Wang, Xia, Clark, Gary D, Bertoli, Marta, Zwolinski, Simon, Thomas, Rhys H, Akay, Ela, Chang, Richard C, Bressi, Rebekah, Sanchez Russo, Rossana, Srour, Myriam, Russell, Laura, Goyette, Anne-Marie E, Dupuis, Lucie, Mendoza-Londono, Roberto, Karimov, Catherine, Joseph, Maries, Nizon, Mathilde, Cogné, Benjamin, Kuechler, Alma, Piton, Amélie, Klee, Eric W, Lefebvre, Véronique, Clark, Karl J, and Depienne, Christel

Subjects
Intellectual and Developmental Disabilities (IDD), Pediatric, Genetics, Brain Disorders, Clinical Research, Rare Diseases, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Animals, Child, Child, Preschool, DNA-Binding Proteins, Female, Genetic Predisposition to Disease, Haploinsufficiency, Humans, Infant, Intellectual Disability, Language Development Disorders, Male, Mutation, Missense, Neurodevelopmental Disorders, Pedigree, Phenotype, SOXD Transcription Factors, Young Adult, autism, developmental delay, intellectual disability, epilepsy, missense variants, Deciphering Developmental DisorderStudy, missense variants., Clinical Sciences, Genetics & Heredity
Abstract

PurposeLamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved.MethodsClinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated.ResultsMicrodeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated.ConclusionsThis study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features.

Published
2020

6. PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights.

Author

Johnstone, Devon L, Al-Shekaili, Hilal H, Tarailo-Graovac, Maja, Wolf, Nicole I, Ivy, Autumn S, Demarest, Scott, Roussel, Yann, Ciapaite, Jolita, van Roermund, Carlo WT, Kernohan, Kristin D, Kosuta, Ceres, Ban, Kevin, Ito, Yoko, McBride, Skye, Al-Thihli, Khalid, Abdelrahim, Rana A, Koul, Roshan, Al Futaisi, Amna, Haaxma, Charlotte A, Olson, Heather, Sigurdardottir, Laufey Yr, Arnold, Georgianne L, Gerkes, Erica H, Boon, M, Heiner-Fokkema, M Rebecca, Noble, Sandra, Bosma, Marjolein, Jans, Judith, Koolen, David A, Kamsteeg, Erik-Jan, Drögemöller, Britt, Ross, Colin J, Majewski, Jacek, Cho, Megan T, Begtrup, Amber, Wasserman, Wyeth W, Bui, Tuan, Brimble, Elise, Violante, Sara, Houten, Sander M, Wevers, Ron A, van Faassen, Martijn, Kema, Ido P, Lepage, Nathalie, Lines, Matthew A, Dyment, David A, Wanders, Ronald JA, Verhoeven-Duif, Nanda, Ekker, Marc, Boycott, Kym M, Friedman, Jan M, Pena, Izabella A, and van Karnebeek, Clara DM

Subjects
Epilepsy, Neurosciences, Brain Disorders, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Neurological, Animals, Disease Models, Animal, Female, HEK293 Cells, Humans, Male, Phenotype, Proteins, Pyridoxal Phosphate, Pyridoxine, Vitamin B 6, Vitamin B 6 Deficiency, Zebrafish, PLPBP, PROSC, epilepsy, pyridoxine, vitamin B6-responsive epilepsy, Care4Rare Canada Consortium, PLPBP, PROSC, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis of which is poorly understood. When left untreated, the disease can progress to status epilepticus and death in infancy. Here we present 12 previously undescribed patients and six novel pathogenic variants in PLPBP. Suspected clinical diagnoses prior to identification of PLPBP variants included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient) and a movement disorder compatible with AADC deficiency (one patient). The encoded protein, PLPHP is believed to be crucial for B6 homeostasis. We modelled the pathogenicity of the variants and developed a clinical severity scoring system. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding. To explore the pathophysiology of this disease further, we developed the first zebrafish model of PLPHP deficiency using CRISPR/Cas9. Our model recapitulates the disease, with plpbp-/- larvae showing behavioural, biochemical, and electrophysiological signs of seizure activity by 10 days post-fertilization and early death by 16 days post-fertilization. Treatment with pyridoxine significantly improved the epileptic phenotype and extended lifespan in plpbp-/- animals. Larvae had disruptions in amino acid metabolism as well as GABA and catecholamine biosynthesis, indicating impairment of PLP-dependent enzymatic activities. Using mass spectrometry, we observed significant B6 vitamer level changes in plpbp-/- zebrafish, patient fibroblasts and PLPHP-deficient HEK293 cells. Additional studies in human cells and yeast provide the first empirical evidence that PLPHP is localized in mitochondria and may play a role in mitochondrial metabolism. These models provide new insights into disease mechanisms and can serve as a platform for drug discovery.

Published
2019

7. Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability.

Author

Cogné, Benjamin, Ehresmann, Sophie, Beauregard-Lacroix, Eliane, Rousseau, Justine, Besnard, Thomas, Garcia, Thomas, Petrovski, Slavé, Avni, Shiri, McWalter, Kirsty, Blackburn, Patrick R, Sanders, Stephan J, Uguen, Kévin, Harris, Jacqueline, Cohen, Julie S, Blyth, Moira, Lehman, Anna, Berg, Jonathan, Li, Mindy H, Kini, Usha, Joss, Shelagh, von der Lippe, Charlotte, Gordon, Christopher T, Humberson, Jennifer B, Robak, Laurie, Scott, Daryl A, Sutton, Vernon R, Skraban, Cara M, Johnston, Jennifer J, Poduri, Annapurna, Nordenskjöld, Magnus, Shashi, Vandana, Gerkes, Erica H, Bongers, Ernie MHF, Gilissen, Christian, Zarate, Yuri A, Kvarnung, Malin, Lally, Kevin P, Kulch, Peggy A, Daniels, Brina, Hernandez-Garcia, Andres, Stong, Nicholas, McGaughran, Julie, Retterer, Kyle, Tveten, Kristian, Sullivan, Jennifer, Geisheker, Madeleine R, Stray-Pedersen, Asbjorg, Tarpinian, Jennifer M, Klee, Eric W, Sapp, Julie C, Zyskind, Jacob, Holla, Øystein L, Bedoukian, Emma, Filippini, Francesca, Guimier, Anne, Picard, Arnaud, Busk, Øyvind L, Punetha, Jaya, Pfundt, Rolph, Lindstrand, Anna, Nordgren, Ann, Kalb, Fayth, Desai, Megha, Ebanks, Ashley Harmon, Jhangiani, Shalini N, Dewan, Tammie, Coban Akdemir, Zeynep H, Telegrafi, Aida, Zackai, Elaine H, Begtrup, Amber, Song, Xiaofei, Toutain, Annick, Wentzensen, Ingrid M, Odent, Sylvie, Bonneau, Dominique, Latypova, Xénia, Deb, Wallid, CAUSES Study, Redon, Sylvia, Bilan, Frédéric, Legendre, Marine, Troyer, Caitlin, Whitlock, Kerri, Caluseriu, Oana, Murphree, Marine I, Pichurin, Pavel N, Agre, Katherine, Gavrilova, Ralitza, Rinne, Tuula, Park, Meredith, Shain, Catherine, Heinzen, Erin L, Xiao, Rui, Amiel, Jeanne, Lyonnet, Stanislas, Isidor, Bertrand, Biesecker, Leslie G, Lowenstein, Dan, Posey, Jennifer E, and Denommé-Pichon, Anne-Sophie

Subjects
CAUSES Study, Deciphering Developmental Disorders study, Humans, Syndrome, Adaptor Proteins, Signal Transducing, Nuclear Proteins, Prognosis, Autistic Disorder, Amino Acid Sequence, Sequence Homology, Mutation, Missense, Adolescent, Adult, Child, Child, Preschool, Infant, Female, Male, Young Adult, Genetic Association Studies, Intellectual Disability, TRRAP, autism spectrum disorder, congenital malformations, de novo variants, histone acetylation, intellectual disability, neurodevelopmental disorders, Intellectual and Developmental Disabilities (IDD), Pediatric, Genetics, Brain Disorders, Neurosciences, Mental Health, Autism, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Mental health, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants.

Published
2019

8. Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON

Author

Dingemans, Alexander J. M., Truijen, Kim M. G., Kim, Jung-Hyun, Alaçam, Zahide, Faivre, Laurence, Collins, Kathleen M., Gerkes, Erica H., van Haelst, Mieke, van de Laar, Ingrid M. B. H., Lindstrom, Kristin, Nizon, Mathilde, Pauling, James, Heropolitańska-Pliszka, Edyta, Plomp, Astrid S., Racine, Caroline, Sachdev, Rani, Sinnema, Margje, Skranes, Jon, Veenstra-Knol, Hermine E., Verberne, Eline A., Vulto-van Silfhout, Anneke T., Wilsterman, Marlon E. F., Ahn, Eun-Young Erin, de Vries, Bert B. A., and Vissers, Lisenka E. L. M.

Published
2022
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9. The phenotypic spectrum and genotype-phenotype correlations in 106 patients with variants in major autism gene CHD8

Author

Dingemans, Alexander J. M., Truijen, Kim M. G., van de Ven, Sam, Bernier, Raphael, Bongers, Ernie M. H. F., Bouman, Arjan, de Graaff – Herder, Laura, Eichler, Evan E., Gerkes, Erica H., De Geus, Christa M., van Hagen, Johanna M., Jansen, Philip R., Kerkhof, Jennifer, Kievit, Anneke J. A., Kleefstra, Tjitske, Maas, Saskia M., de Man, Stella A., McConkey, Haley, Patterson, Wesley G., Dobson, Amy T., Prijoles, Eloise J., Sadikovic, Bekim, Relator, Raissa, Stevenson, Roger E., Stumpel, Connie T. R. M., Heijligers, Malou, Stuurman, Kyra E., Löhner, Katharina, Zeidler, Shimriet, Lee, Jennifer A., Lindy, Amanda, Zou, Fanggeng, Tedder, Matthew L., Vissers, Lisenka E. L. M., and de Vries, Bert B. A.

Published
2022
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10. CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Author

Gehin, Charlotte, Lone, Museer A., Lee, Winston, Capolupo, Laura, Ho, Sylvia, Adeyemi, Adekemi M., Gerkes, Erica H., Stegmann, Alexander P.A., Lopez-Martin, Estrella, and Bermejo-Sanchez, Eva

Subjects
Gene mutations -- Physiological aspects -- Health aspects, Sphingolipids -- Physiological aspects -- Health aspects, Mental retardation -- Risk factors -- Development and progression -- Genetic aspects, Carrier proteins -- Genetic aspects -- Health aspects, Pediatric research, Health care industry
Abstract

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome., Introduction Sphingolipids play numerous essential roles in membrane structure, signal transduction, and brain development and function (1-3). The central nervous system is particularly affected by disturbances in sphingolipid production or [...]

Published
2023
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11. Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes

Author

Staf strategisch beleid, Genetica Klinische Genetica, Child Health, Rots, Dmitrijs, Choufani, Sanaa, Faundes, Victor, Dingemans, Alexander J.M., Joss, Shelagh, Foulds, Nicola, Jones, Elizabeth A., Stewart, Sarah, Vasudevan, Pradeep, Dabir, Tabib, Park, Soo Mi, Jewell, Rosalyn, Brown, Natasha, Pais, Lynn, Jacquemont, Sébastien, Jizi, Khadijé, Ravenswaaij-Arts, Conny M.A.van, Kroes, Hester Y., Stumpel, Constance T.R.M., Ockeloen, Charlotte W., Diets, Illja J., Nizon, Mathilde, Vincent, Marie, Cogné, Benjamin, Besnard, Thomas, Kambouris, Marios, Anderson, Emily, Zackai, Elaine H., McDougall, Carey, Donoghue, Sarah, O'Donnell-Luria, Anne, Valivullah, Zaheer, O'Leary, Melanie, Srivastava, Siddharth, Byers, Heather, Leslie, Nancy, Mazzola, Sarah, Tiller, George E., Vera, Moin, Shen, Joseph J., Boles, Richard, Jain, Vani, Brischoux-Boucher, Elise, Kinning, Esther, Simpson, Brittany N., Giltay, Jacques C., Harris, Jacqueline, Keren, Boris, Guimier, Anne, Marijon, Pierre, de Vries, Bert B.A., Motter, Constance S., Mendelsohn, Bryce A., Coffino, Samantha, Gerkes, Erica H., Afenjar, Alexandra, Visconti, Paola, Bacchelli, Elena, Maestrini, Elena, Delahaye-Duriez, Andree, Gooch, Catherine, Hendriks, Yvonne, Adams, Hieab, Thauvin-Robinet, Christel, Josephi-Taylor, Sarah, Bertoli, Marta, Parker, Michael J., Rutten, Julie W., Caluseriu, Oana, Vernon, Hilary J., Kaziyev, Jonah, Zhu, Jia, Kremen, Jessica, Frazier, Zoe, Osika, Hailey, Breault, David, Nair, Sreelata, Lewis, Suzanne M.E., Ceroni, Fabiola, Viggiano, Marta, Posar, Annio, Brittain, Helen, Giovanna, Traficante, Giulia, Gori, Quteineh, Lina, Ha-Vinh Leuchter, Russia, Zonneveld-Huijssoon, Evelien, Mellado, Cecilia, Marey, Isabelle, Coudert, Alicia, Aracena Alvarez, Mariana Inés, Kennis, Milou G.P., Bouman, Arianne, Roifman, Maian, Amorós Rodríguez, María Inmaculada, Ortigoza-Escobar, Juan Dario, Vernimmen, Vivian, Sinnema, Margje, Pfundt, Rolph, Brunner, Han G., Vissers, Lisenka E.L.M., Kleefstra, Tjitske, Weksberg, Rosanna, Banka, Siddharth, Staf strategisch beleid, Genetica Klinische Genetica, Child Health, Rots, Dmitrijs, Choufani, Sanaa, Faundes, Victor, Dingemans, Alexander J.M., Joss, Shelagh, Foulds, Nicola, Jones, Elizabeth A., Stewart, Sarah, Vasudevan, Pradeep, Dabir, Tabib, Park, Soo Mi, Jewell, Rosalyn, Brown, Natasha, Pais, Lynn, Jacquemont, Sébastien, Jizi, Khadijé, Ravenswaaij-Arts, Conny M.A.van, Kroes, Hester Y., Stumpel, Constance T.R.M., Ockeloen, Charlotte W., Diets, Illja J., Nizon, Mathilde, Vincent, Marie, Cogné, Benjamin, Besnard, Thomas, Kambouris, Marios, Anderson, Emily, Zackai, Elaine H., McDougall, Carey, Donoghue, Sarah, O'Donnell-Luria, Anne, Valivullah, Zaheer, O'Leary, Melanie, Srivastava, Siddharth, Byers, Heather, Leslie, Nancy, Mazzola, Sarah, Tiller, George E., Vera, Moin, Shen, Joseph J., Boles, Richard, Jain, Vani, Brischoux-Boucher, Elise, Kinning, Esther, Simpson, Brittany N., Giltay, Jacques C., Harris, Jacqueline, Keren, Boris, Guimier, Anne, Marijon, Pierre, de Vries, Bert B.A., Motter, Constance S., Mendelsohn, Bryce A., Coffino, Samantha, Gerkes, Erica H., Afenjar, Alexandra, Visconti, Paola, Bacchelli, Elena, Maestrini, Elena, Delahaye-Duriez, Andree, Gooch, Catherine, Hendriks, Yvonne, Adams, Hieab, Thauvin-Robinet, Christel, Josephi-Taylor, Sarah, Bertoli, Marta, Parker, Michael J., Rutten, Julie W., Caluseriu, Oana, Vernon, Hilary J., Kaziyev, Jonah, Zhu, Jia, Kremen, Jessica, Frazier, Zoe, Osika, Hailey, Breault, David, Nair, Sreelata, Lewis, Suzanne M.E., Ceroni, Fabiola, Viggiano, Marta, Posar, Annio, Brittain, Helen, Giovanna, Traficante, Giulia, Gori, Quteineh, Lina, Ha-Vinh Leuchter, Russia, Zonneveld-Huijssoon, Evelien, Mellado, Cecilia, Marey, Isabelle, Coudert, Alicia, Aracena Alvarez, Mariana Inés, Kennis, Milou G.P., Bouman, Arianne, Roifman, Maian, Amorós Rodríguez, María Inmaculada, Ortigoza-Escobar, Juan Dario, Vernimmen, Vivian, Sinnema, Margje, Pfundt, Rolph, Brunner, Han G., Vissers, Lisenka E.L.M., Kleefstra, Tjitske, Weksberg, Rosanna, and Banka, Siddharth

Published
2024

12. The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

Author

Koolen, David A, Pfundt, Rolph, Linda, Katrin, Beunders, Gea, Veenstra-Knol, Hermine E, Conta, Jessie H, Fortuna, Ana Maria, Gillessen-Kaesbach, Gabriele, Dugan, Sarah, Halbach, Sara, Abdul-Rahman, Omar A, Winesett, Heather M, Chung, Wendy K, Dalton, Marguerite, Dimova, Petia S, Mattina, Teresa, Prescott, Katrina, Zhang, Hui Z, Saal, Howard M, Hehir-Kwa, Jayne Y, Willemsen, Marjolein H, Ockeloen, Charlotte W, Jongmans, Marjolijn C, Van der Aa, Nathalie, Failla, Pinella, Barone, Concetta, Avola, Emanuela, Brooks, Alice S, Kant, Sarina G, Gerkes, Erica H, Firth, Helen V, Õunap, Katrin, Bird, Lynne M, Masser-Frye, Diane, Friedman, Jennifer R, Sokunbi, Modupe A, Dixit, Abhijit, Splitt, Miranda, Kukolich, Mary K, McGaughran, Julie, Coe, Bradley P, Flórez, Jesús, Nadif Kasri, Nael, Brunner, Han G, Thompson, Elizabeth M, Gecz, Jozef, Romano, Corrado, Eichler, Evan E, and de Vries, Bert BA

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Rare Diseases, Pediatric, Neurosciences, Congenital Structural Anomalies, Brain Disorders, Clinical Research, Intellectual and Developmental Disabilities (IDD), Aetiology, 2.1 Biological and endogenous factors, Congenital, Abnormalities, Multiple, Adolescent, Adult, Child, Chromosome Deletion, Chromosomes, Human, Pair 17, Female, Humans, Intellectual Disability, Male, Middle Aged, Nuclear Proteins, Phenotype, Polymorphism, Single Nucleotide, DDD Study, Clinical Sciences, Genetics & Heredity, Clinical sciences
Abstract

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

Published
2016

15. The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Author

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.

Published
2019
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17. Supplementary Appendix 2 from High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Author

Diets, Illja J., primary, Waanders, Esmé, primary, Ligtenberg, Marjolijn J., primary, van Bladel, Diede A.G., primary, Kamping, Eveline J., primary, Hoogerbrugge, Peter M., primary, Hopman, Saskia, primary, Olderode-Berends, Maran J., primary, Gerkes, Erica H., primary, Koolen, David A., primary, Marcelis, Carlo, primary, Santen, Gijs W., primary, van Belzen, Martine J., primary, Mordaunt, Dylan, primary, McGregor, Lesley, primary, Thompson, Elizabeth, primary, Kattamis, Antonis, primary, Pastorczak, Agata, primary, Mlynarski, Wojciech, primary, Ilencikova, Denisa, primary, van Silfhout, Anneke Vulto-, primary, Gardeitchik, Thatjana, primary, de Bont, Eveline S., primary, Loeffen, Jan, primary, Wagner, Anja, primary, Mensenkamp, Arjen R., primary, Kuiper, Roland P., primary, Hoogerbrugge, Nicoline, primary, and Jongmans, Marjolijn C., primary

Published
2023
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18. Supplementary Appendix 1 from High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Author

Diets, Illja J., primary, Waanders, Esmé, primary, Ligtenberg, Marjolijn J., primary, van Bladel, Diede A.G., primary, Kamping, Eveline J., primary, Hoogerbrugge, Peter M., primary, Hopman, Saskia, primary, Olderode-Berends, Maran J., primary, Gerkes, Erica H., primary, Koolen, David A., primary, Marcelis, Carlo, primary, Santen, Gijs W., primary, van Belzen, Martine J., primary, Mordaunt, Dylan, primary, McGregor, Lesley, primary, Thompson, Elizabeth, primary, Kattamis, Antonis, primary, Pastorczak, Agata, primary, Mlynarski, Wojciech, primary, Ilencikova, Denisa, primary, van Silfhout, Anneke Vulto-, primary, Gardeitchik, Thatjana, primary, de Bont, Eveline S., primary, Loeffen, Jan, primary, Wagner, Anja, primary, Mensenkamp, Arjen R., primary, Kuiper, Roland P., primary, Hoogerbrugge, Nicoline, primary, and Jongmans, Marjolijn C., primary

Published
2023
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19. CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Author

Genetica Klinische Genetica, Brain, Child Health, Gehin, Charlotte, Lone, Museer A, Lee, Winston, Capolupo, Laura, Ho, Sylvia, Adeyemi, Adekemi M, Gerkes, Erica H, Stegmann, Alexander Pa, López-Martín, Estrella, Bermejo-Sánchez, Eva, Martínez-Delgado, Beatriz, Zweier, Christiane, Kraus, Cornelia, Popp, Bernt, Strehlow, Vincent, Gräfe, Daniel, Knerr, Ina, Jones, Eppie R, Zamuner, Stefano, Abriata, Luciano A, Kunnathully, Vidya, Moeller, Brandon E, Vocat, Anthony, Rommelaere, Samuel, Bocquete, Jean-Philippe, Ruchti, Evelyne, Limoni, Greta, Van Campenhoudt, Marine, Bourgeat, Samuel, Henklein, Petra, Gilissen, Christian, van Bon, Bregje W, Pfundt, Rolph, Willemsen, Marjolein H, Schieving, Jolanda H, Leonardi, Emanuela, Soli, Fiorenza, Murgia, Alessandra, Guo, Hui, Zhang, Qiumeng, Xia, Kun, Fagerberg, Christina R, Beier, Christoph P, Larsen, Martin J, Valenzuela, Irene, Fernández-Álvarez, Paula, Xiong, Shiyi, Śmigiel, Robert, López-González, Vanesa, Armengol, Lluís, Morleo, Manuela, Selicorni, Angelo, Torella, Annalaura, Blyth, Moira, Cooper, Nicola S, Wilson, Valerie, Oegema, Renske, Herenger, Yvan, Garde, Aurore, Bruel, Ange-Line, Tran Mau-Them, Frederic, Maddocks, Alexis Br, Bain, Jennifer M, Bhat, Musadiq A, Costain, Gregory, Kannu, Peter, Marwaha, Ashish, Champaigne, Neena L, Friez, Michael J, Richardson, Ellen B, Gowda, Vykuntaraju K, Srinivasan, Varunvenkat M, Gupta, Yask, Lim, Tze Y, Sanna-Cherchi, Simone, Lemaitre, Bruno, Yamaji, Toshiyuki, Hanada, Kentaro, Burke, John E, Jakšić, Ana Marija, McCabe, Brian D, De Los Rios, Paolo, Hornemann, Thorsten, D'Angelo, Giovanni, Gennarino, Vincenzo A, Genetica Klinische Genetica, Brain, Child Health, Gehin, Charlotte, Lone, Museer A, Lee, Winston, Capolupo, Laura, Ho, Sylvia, Adeyemi, Adekemi M, Gerkes, Erica H, Stegmann, Alexander Pa, López-Martín, Estrella, Bermejo-Sánchez, Eva, Martínez-Delgado, Beatriz, Zweier, Christiane, Kraus, Cornelia, Popp, Bernt, Strehlow, Vincent, Gräfe, Daniel, Knerr, Ina, Jones, Eppie R, Zamuner, Stefano, Abriata, Luciano A, Kunnathully, Vidya, Moeller, Brandon E, Vocat, Anthony, Rommelaere, Samuel, Bocquete, Jean-Philippe, Ruchti, Evelyne, Limoni, Greta, Van Campenhoudt, Marine, Bourgeat, Samuel, Henklein, Petra, Gilissen, Christian, van Bon, Bregje W, Pfundt, Rolph, Willemsen, Marjolein H, Schieving, Jolanda H, Leonardi, Emanuela, Soli, Fiorenza, Murgia, Alessandra, Guo, Hui, Zhang, Qiumeng, Xia, Kun, Fagerberg, Christina R, Beier, Christoph P, Larsen, Martin J, Valenzuela, Irene, Fernández-Álvarez, Paula, Xiong, Shiyi, Śmigiel, Robert, López-González, Vanesa, Armengol, Lluís, Morleo, Manuela, Selicorni, Angelo, Torella, Annalaura, Blyth, Moira, Cooper, Nicola S, Wilson, Valerie, Oegema, Renske, Herenger, Yvan, Garde, Aurore, Bruel, Ange-Line, Tran Mau-Them, Frederic, Maddocks, Alexis Br, Bain, Jennifer M, Bhat, Musadiq A, Costain, Gregory, Kannu, Peter, Marwaha, Ashish, Champaigne, Neena L, Friez, Michael J, Richardson, Ellen B, Gowda, Vykuntaraju K, Srinivasan, Varunvenkat M, Gupta, Yask, Lim, Tze Y, Sanna-Cherchi, Simone, Lemaitre, Bruno, Yamaji, Toshiyuki, Hanada, Kentaro, Burke, John E, Jakšić, Ana Marija, McCabe, Brian D, De Los Rios, Paolo, Hornemann, Thorsten, D'Angelo, Giovanni, and Gennarino, Vincenzo A

Published
2023

20. CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Author

Gehin, Charlotte; https://orcid.org/0000-0003-1164-2968, Lone, Museer A; https://orcid.org/0000-0001-9710-775X, Lee, Winston, Capolupo, Laura; https://orcid.org/0000-0003-1254-5019, Ho, Sylvia; https://orcid.org/0000-0002-2969-7329, Adeyemi, Adekemi M, Gerkes, Erica H, Stegmann, Alexander P A; https://orcid.org/0000-0002-9736-7137, López-Martín, Estrella, Bermejo-Sánchez, Eva; https://orcid.org/0000-0001-7282-2714, Martínez-Delgado, Beatriz, Zweier, Christiane, Kraus, Cornelia, Popp, Bernt; https://orcid.org/0000-0002-3679-1081, Strehlow, Vincent; https://orcid.org/0000-0003-1361-7766, Gräfe, Daniel; https://orcid.org/0000-0002-7680-0990, Knerr, Ina; https://orcid.org/0000-0002-4015-0658, Jones, Eppie R, Zamuner, Stefano, Abriata, Luciano A, Kunnathully, Vidya, Moeller, Brandon E, Vocat, Anthony, Rommelaere, Samuel, Bocquete, Jean-Philippe, Ruchti, Evelyne; https://orcid.org/0000-0003-1211-2336, Limoni, Greta; https://orcid.org/0000-0002-6808-9510, Van Campenhoudt, Marine, Bourgeat, Samuel; https://orcid.org/0000-0001-6038-0226, Henklein, Petra; https://orcid.org/0000-0001-7468-8926, et al, Hornemann, Thorsten, Bhat, Musadiq A; https://orcid.org/0000-0002-0894-9996, Gehin, Charlotte; https://orcid.org/0000-0003-1164-2968, Lone, Museer A; https://orcid.org/0000-0001-9710-775X, Lee, Winston, Capolupo, Laura; https://orcid.org/0000-0003-1254-5019, Ho, Sylvia; https://orcid.org/0000-0002-2969-7329, Adeyemi, Adekemi M, Gerkes, Erica H, Stegmann, Alexander P A; https://orcid.org/0000-0002-9736-7137, López-Martín, Estrella, Bermejo-Sánchez, Eva; https://orcid.org/0000-0001-7282-2714, Martínez-Delgado, Beatriz, Zweier, Christiane, Kraus, Cornelia, Popp, Bernt; https://orcid.org/0000-0002-3679-1081, Strehlow, Vincent; https://orcid.org/0000-0003-1361-7766, Gräfe, Daniel; https://orcid.org/0000-0002-7680-0990, Knerr, Ina; https://orcid.org/0000-0002-4015-0658, Jones, Eppie R, Zamuner, Stefano, Abriata, Luciano A, Kunnathully, Vidya, Moeller, Brandon E, Vocat, Anthony, Rommelaere, Samuel, Bocquete, Jean-Philippe, Ruchti, Evelyne; https://orcid.org/0000-0003-1211-2336, Limoni, Greta; https://orcid.org/0000-0002-6808-9510, Van Campenhoudt, Marine, Bourgeat, Samuel; https://orcid.org/0000-0001-6038-0226, Henklein, Petra; https://orcid.org/0000-0001-7468-8926, et al, Hornemann, Thorsten, and Bhat, Musadiq A; https://orcid.org/0000-0002-0894-9996

Abstract

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome.

Published
2023

21. Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Author

Arts, Peer, Simons, Annet, AlZahrani, Mofareh S., Yilmaz, Elanur, AlIdrissi, Eman, van Aerde, Koen J., Alenezi, Njood, AlGhamdi, Hamza A., AlJubab, Hadeel A., Al-Hussaini, Abdulrahman A., AlManjomi, Fahad, Alsaad, Alaa B., Alsaleem, Badr, Andijani, Abdulrahman A., Asery, Ali, Ballourah, Walid, Bleeker-Rovers, Chantal P., van Deuren, Marcel, van der Flier, Michiel, Gerkes, Erica H., Gilissen, Christian, Habazi, Murad K., Hehir-Kwa, Jayne Y., Henriet, Stefanie S., Hoppenreijs, Esther P., Hortillosa, Sarah, Kerkhofs, Chantal H., Keski-Filppula, Riikka, Lelieveld, Stefan H., Lone, Khurram, MacKenzie, Marius A., Mensenkamp, Arjen R., Moilanen, Jukka, Nelen, Marcel, ten Oever, Jaap, Potjewijd, Judith, van Paassen, Pieter, Schuurs-Hoeijmakers, Janneke H. M., Simon, Anna, Stokowy, Tomasz, van de Vorst, Maartje, Vreeburg, Maaike, Wagner, Anja, van Well, Gijs T. J., Zafeiropoulou, Dimitra, Zonneveld-Huijssoon, Evelien, Veltman, Joris A., van Zelst-Stams, Wendy A. G., Faqeih, Eissa A., van de Veerdonk, Frank L., Netea, Mihai G., and Hoischen, Alexander

Published
2019
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22. Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort

Author

van der Sluijs, Pleuntje J., primary, Joosten, Marieke, additional, Alby, Caroline, additional, Attié-Bitach, Tania, additional, Gilmore, Kelly, additional, Dubourg, Christele, additional, Fradin, Mélanie, additional, Wang, Tianyun, additional, Kurtz-Nelson, Evangeline C., additional, Ahlers, Kaitlyn P., additional, Arts, Peer, additional, Barnett, Christopher P., additional, Ashfaq, Myla, additional, Baban, Anwar, additional, van den Born, Myrthe, additional, Borrie, Sarah, additional, Busa, Tiffany, additional, Byrne, Alicia, additional, Carriero, Miriam, additional, Cesario, Claudia, additional, Chong, Karen, additional, Cueto-González, Anna Maria, additional, Dempsey, Jennifer C., additional, Diderich, Karin E.M., additional, Doherty, Dan, additional, Farholt, Stense, additional, Gerkes, Erica H., additional, Gorokhova, Svetlana, additional, Govaerts, Lutgarde C.P., additional, Gregersen, Pernille A., additional, Hickey, Scott E., additional, Lefebvre, Mathilde, additional, Mari, Francesca, additional, Martinovic, Jelena, additional, Northrup, Hope, additional, O’Leary, Melanie, additional, Parbhoo, Kareesma, additional, Patrier, Sophie, additional, Popp, Bernt, additional, Santos-Simarro, Fernando, additional, Stoltenburg, Corinna, additional, Thauvin-Robinet, Christel, additional, Thompson, Elisabeth, additional, Vulto-van Silfhout, Anneke T., additional, Zahir, Farah R., additional, Scott, Hamish S., additional, Earl, Rachel K., additional, Eichler, Evan E., additional, Vora, Neeta L., additional, Wilnai, Yael, additional, Giordano, Jessica L., additional, Wapner, Ronald J., additional, Rosenfeld, Jill A., additional, Haak, Monique C., additional, and Santen, Gijs W.E., additional

Published
2023
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23. Amniotic band syndrome and limb body wall complex in Europe 1980–2019

Author

Bergman, Jorieke E. H., primary, Barišić, Ingeborg, additional, Addor, Marie‐Claude, additional, Braz, Paula, additional, Cavero‐Carbonell, Clara, additional, Draper, Elizabeth S., additional, Echevarría‐González‐de‐Garibay, Luis J., additional, Gatt, Miriam, additional, Haeusler, Martin, additional, Khoshnood, Babak, additional, Klungsøyr, Kari, additional, Kurinczuk, Jennifer J., additional, Latos‐Bielenska, Anna, additional, Luyt, Karen, additional, Martin, Danielle, additional, Mullaney, Carmel, additional, Nelen, Vera, additional, Neville, Amanda J., additional, O'Mahony, Mary T., additional, Perthus, Isabelle, additional, Pierini, Anna, additional, Randrianaivo, Hanitra, additional, Rankin, Judith, additional, Rissmann, Anke, additional, Rouget, Florence, additional, Sayers, Gerardine, additional, Schaub, Bruno, additional, Stevens, Sarah, additional, Tucker, David, additional, Verellen‐Dumoulin, Christine, additional, Wiesel, Awi, additional, Gerkes, Erica H., additional, Perraud, Annie, additional, Loane, Maria A., additional, Wellesley, Diana, additional, and de Walle, Hermien E. K., additional

Published
2022
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24. Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability

Author

Bramswig, Nuria C., Lüdecke, Hermann-Josef, Hamdan, Fadi F., Altmüller, Janine, Beleggia, Filippo, Elcioglu, Nursel H., Freyer, Catharine, Gerkes, Erica H., Demirkol, Yasemin Kendir, Knupp, Kelly G., Kuechler, Alma, Li, Yun, Lowenstein, Daniel H., Michaud, Jacques L., Park, Kristen, Stegmann, Alexander P.A., Veenstra-Knol, Hermine E., Wieland, Thomas, Wollnik, Bernd, Engels, Hartmut, Strom, Tim M., Kleefstra, Tjitske, and Wieczorek, Dagmar

Published
2017
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25. Correction: The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Author

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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26. Loss-of-function variants in SRRM2 cause a neurodevelopmental disorder

Author

Cuinat, Silvestre, primary, Nizon, Mathilde, additional, Isidor, Bertrand, additional, Stegmann, Alexander, additional, van Jaarsveld, Richard H., additional, van Gassen, Koen L., additional, van der Smagt, Jasper J., additional, Volker-Touw, Catharina M.L., additional, Holwerda, Sjoerd J.B., additional, Terhal, Paulien A., additional, Schuhmann, Sarah, additional, Vasileiou, Georgia, additional, Khalifa, Mohamed, additional, Nugud, Alaa A., additional, Yasaei, Hemad, additional, Ousager, Lilian Bomme, additional, Brasch-Andersen, Charlotte, additional, Deb, Wallid, additional, Besnard, Thomas, additional, Simon, Marleen E.H., additional, Amsterdam, Karin Huijsdens-van, additional, Verbeek, Nienke E., additional, Matalon, Dena, additional, Dykzeul, Natalie, additional, White, Shana, additional, Spiteri, Elizabeth, additional, Devriendt, Koen, additional, Boogaerts, Anneleen, additional, Willemsen, Marjolein, additional, Brunner, Han G., additional, Sinnema, Margje, additional, De Vries, Bert B.A., additional, Gerkes, Erica H., additional, Pfundt, Rolph, additional, Izumi, Kosuke, additional, Krantz, Ian D., additional, Xu, Zhou L., additional, Murrell, Jill R., additional, Valenzuela, Irene, additional, Cusco, Ivon, additional, Rovira-Moreno, Eulàlia, additional, Yang, Yaping, additional, Bizaoui, Varoona, additional, Patat, Olivier, additional, Faivre, Laurence, additional, Tran-Mau-Them, Frederic, additional, Vitobello, Antonio, additional, Denommé-Pichon, Anne-Sophie, additional, Philippe, Christophe, additional, Bezieau, Stéphane, additional, and Cogné, Benjamin, additional

Published
2022
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27. Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort

Author

van der Sluijs, Pleuntje J., primary, Joosten, Marieke, additional, Alby, Caroline, additional, Attié-Bitach, Tania, additional, Gilmore, Kelly, additional, Dubourg, Christele, additional, Fradin, Mélanie, additional, Wang, Tianyun, additional, Kurtz-Nelson, Evangeline C., additional, Ahlers, Kaitlyn P., additional, Arts, Peer, additional, Barnett, Christopher P., additional, Ashfaq, Myla, additional, Baban, Anwar, additional, van den Born, Myrthe, additional, Borrie, Sarah, additional, Busa, Tiffany, additional, Byrne, Alicia, additional, Carriero, Miriam, additional, Cesario, Claudia, additional, Chong, Karen, additional, Cueto-González, Anna Maria, additional, Dempsey, Jennifer C., additional, Diderich, Karin E.M., additional, Doherty, Dan, additional, Farholt, Stense, additional, Gerkes, Erica H., additional, Gorokhova, Svetlana, additional, Govaerts, Lutgarde C.P., additional, Gregersen, Pernille A., additional, Hickey, Scott E., additional, Lefebvre, Mathilde, additional, Mari, Francesca, additional, Martinovic, Jelena, additional, Northrup, Hope, additional, O’Leary, Melanie, additional, Parbhoo, Kareesma, additional, Patrier, Sophie, additional, Popp, Bernt, additional, Santos-Simarro, Fernando, additional, Stoltenburg, Corinna, additional, Thauvin-Robinet, Christel, additional, Thompson, Elisabeth, additional, Vulto-van Silfhout, Anneke T., additional, Zahir, Farah R., additional, Scott, Hamish S., additional, Earl, Rachel K., additional, Eichler, Evan E., additional, Vora, Neeta L., additional, Wilnai, Yael, additional, Giordano, Jessica L., additional, Wapner, Ronald J., additional, Rosenfeld, Jill A., additional, Haak, Monique C., additional, and Santen, Gijs W.E., additional

Published
2022
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28. Further delineation of auriculocondylar syndrome based on 14 novel cases and reassessment of 25 published cases.

Author

UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Centre de malformations vasculaires congénitales, UCL - (SLuc) Centre de génétique médicale UCL, Vegas, Nancy, Demir, Zeynep, Gordon, Christopher T, Breton, Sylvain, Romanelli Tavares, Vanessa L, Moisset, Hugo, Zechi-Ceide, Roseli, Kokitsu-Nakata, Nancy M, Kido, Yasuhiro, Marlin, Sandrine, Gherbi Halem, Souad, Meerschaut, Ilse, Callewaert, Bert, Chung, Brian, Revencu, Nicole, Lehalle, Daphné, Petit, Florence, Propst, Evan J, Papsin, Blake C, Phillips, John H, Jakobsen, Linda, Le Tanno, Pauline, Thévenon, Julien, McGaughran, Julie, Gerkes, Erica H, Leoni, Chiara, Kroisel, Peter, Tan, Tiong Y, Henderson, Alex, Terhal, Paulien, Basel-Salmon, Lina, Alkindy, Adila, White, Susan M, Passos-Bueno, Maria R, Pingault, Véronique, De Pontual, Loïc, Amiel, Jeanne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Centre de malformations vasculaires congénitales, UCL - (SLuc) Centre de génétique médicale UCL, Vegas, Nancy, Demir, Zeynep, Gordon, Christopher T, Breton, Sylvain, Romanelli Tavares, Vanessa L, Moisset, Hugo, Zechi-Ceide, Roseli, Kokitsu-Nakata, Nancy M, Kido, Yasuhiro, Marlin, Sandrine, Gherbi Halem, Souad, Meerschaut, Ilse, Callewaert, Bert, Chung, Brian, Revencu, Nicole, Lehalle, Daphné, Petit, Florence, Propst, Evan J, Papsin, Blake C, Phillips, John H, Jakobsen, Linda, Le Tanno, Pauline, Thévenon, Julien, McGaughran, Julie, Gerkes, Erica H, Leoni, Chiara, Kroisel, Peter, Tan, Tiong Y, Henderson, Alex, Terhal, Paulien, Basel-Salmon, Lina, Alkindy, Adila, White, Susan M, Passos-Bueno, Maria R, Pingault, Véronique, De Pontual, Loïc, and Amiel, Jeanne

Abstract

Auriculocondylar syndrome (ACS) is a rare craniofacial disorder characterized by mandibular hypoplasia and an auricular defect at the junction between the lobe and helix, known as a "Question Mark Ear" (QME). Several additional features, originating from the first and second branchial arches and other tissues, have also been reported. ACS is genetically heterogeneous with autosomal dominant and recessive modes of inheritance. The mutations identified to date are presumed to dysregulate the endothelin 1 signaling pathway. Here we describe 14 novel cases and reassess 25 published cases of ACS through a questionnaire for systematic data collection. All patients harbor mutation(s) in PLCB4, GNAI3, or EDN1. This series of patients contributes to the characterization of additional features occasionally associated with ACS such as respiratory, costal, neurodevelopmental, and genital anomalies, and provides management and monitoring recommendations.

Published
2022

29. Further delineation of auriculocondylar syndrome based on 14 novel cases and reassessment of 25 published cases

Author

Vegas, Nancy, Demir, Zeynep, Gordon, Christopher T., Breton, Sylvain, Romanelli Tavares, Vanessa L., Moisset, Hugo, Zechi-Ceide, Roseli, Kokitsu-Nakata, Nancy M., Kido, Yasuhiro, Marlin, Sandrine, Gherbi Halem, Souad, Meerschaut, Ilse, Callewaert, Bert, Chung, Brian, Revencu, Nicole, Lehalle, Daphné, Petit, Florence, Propst, Evan J., Papsin, Blake C., Phillips, John H., Jakobsen, Linda, Le Tanno, Pauline, Thévenon, Julien, McGaughran, Julie, Gerkes, Erica H., Leoni, Chiara, Kroisel, Peter, Tan, Tiong Y., Henderson, Alex, Terhal, Paulien, Basel-Salmon, Lina, Alkindy, Adila, White, Susan M., Passos-Bueno, Maria R., Pingault, Véronique, De Pontual, Loïc, Amiel, Jeanne, Vegas, Nancy, Demir, Zeynep, Gordon, Christopher T., Breton, Sylvain, Romanelli Tavares, Vanessa L., Moisset, Hugo, Zechi-Ceide, Roseli, Kokitsu-Nakata, Nancy M., Kido, Yasuhiro, Marlin, Sandrine, Gherbi Halem, Souad, Meerschaut, Ilse, Callewaert, Bert, Chung, Brian, Revencu, Nicole, Lehalle, Daphné, Petit, Florence, Propst, Evan J., Papsin, Blake C., Phillips, John H., Jakobsen, Linda, Le Tanno, Pauline, Thévenon, Julien, McGaughran, Julie, Gerkes, Erica H., Leoni, Chiara, Kroisel, Peter, Tan, Tiong Y., Henderson, Alex, Terhal, Paulien, Basel-Salmon, Lina, Alkindy, Adila, White, Susan M., Passos-Bueno, Maria R., Pingault, Véronique, De Pontual, Loïc, and Amiel, Jeanne

Abstract

Auriculocondylar syndrome (ACS) is a rare craniofacial disorder characterized by mandibular hypoplasia and an auricular defect at the junction between the lobe and helix, known as a “Question Mark Ear” (QME). Several additional features, originating from the first and second branchial arches and other tissues, have also been reported. ACS is genetically heterogeneous with autosomal dominant and recessive modes of inheritance. The mutations identified to date are presumed to dysregulate the endothelin 1 signaling pathway. Here we describe 14 novel cases and reassess 25 published cases of ACS through a questionnaire for systematic data collection. All patients harbor mutation(s) in PLCB4, GNAI3, or EDN1. This series of patients contributes to the characterization of additional features occasionally associated with ACS such as respiratory, costal, neurodevelopmental, and genital anomalies, and provides management and monitoring recommendations.

Published
2022

30. The phenotypic spectrum and genotype-phenotype correlations in 106 patients with variants in major autism gene CHD8

Author

Dingemans, Alexander J.M., Truijen, Kim M.G., van de Ven, Sam, Bernier, Raphael, Bongers, Ernie M.H.F., Bouman, Arjan, de Graaff – Herder, Laura, Eichler, Evan E., Gerkes, Erica H., De Geus, Christa M., van Hagen, Johanna M., Jansen, Philip R., Kerkhof, Jennifer, Kievit, Anneke J.A., Kleefstra, Tjitske, Maas, Saskia M., de Man, Stella A., McConkey, Haley, Patterson, Wesley G., Dobson, Amy T., Prijoles, Eloise J., Sadikovic, Bekim, Relator, Raissa, Stevenson, Roger E., Stumpel, Connie T.R.M., Heijligers, Malou, Stuurman, Kyra E., Löhner, Katharina, Zeidler, Shimriet, Lee, Jennifer A., Lindy, Amanda, Zou, Fanggeng, Tedder, Matthew L., Vissers, Lisenka E.L.M., de Vries, Bert B.A., Dingemans, Alexander J.M., Truijen, Kim M.G., van de Ven, Sam, Bernier, Raphael, Bongers, Ernie M.H.F., Bouman, Arjan, de Graaff – Herder, Laura, Eichler, Evan E., Gerkes, Erica H., De Geus, Christa M., van Hagen, Johanna M., Jansen, Philip R., Kerkhof, Jennifer, Kievit, Anneke J.A., Kleefstra, Tjitske, Maas, Saskia M., de Man, Stella A., McConkey, Haley, Patterson, Wesley G., Dobson, Amy T., Prijoles, Eloise J., Sadikovic, Bekim, Relator, Raissa, Stevenson, Roger E., Stumpel, Connie T.R.M., Heijligers, Malou, Stuurman, Kyra E., Löhner, Katharina, Zeidler, Shimriet, Lee, Jennifer A., Lindy, Amanda, Zou, Fanggeng, Tedder, Matthew L., Vissers, Lisenka E.L.M., and de Vries, Bert B.A.

Abstract

CHD8, a major autism gene, functions in chromatin remodelling and has various roles involving several biological pathways. Therefore, unsurprisingly, previous studies have shown that intellectual developmental disorder with autism and macrocephaly (IDDAM), the syndrome caused by pathogenic variants in CHD8, consists of a broad range of phenotypic abnormalities. We collected and reviewed 106 individuals with IDDAM, including 36 individuals not previously published, thus enabling thorough genotype–phenotype analyses, involving the CHD8 mutation spectrum, characterization of the CHD8 DNA methylation episignature, and the systematic analysis of phenotypes collected in Human Phenotype Ontology (HPO). We identified 29 unique nonsense, 25 frameshift, 24 missense, and 12 splice site variants. Furthermore, two unique inframe deletions, one larger deletion (exons 26–28), and one translocation were observed. Methylation analysis was performed for 13 patients, 11 of which showed the previously established episignature for IDDAM (85%) associated with CHD8 haploinsufficiency, one analysis was inconclusive, and one showing a possible gain-of-function signature instead of the expected haploinsufficiency signature was observed. Consistent with previous studies, phenotypical abnormalities affected multiple organ systems. Many neurological abnormalities, like intellectual disability (68%) and hypotonia (29%) were observed, as well as a wide variety of behavioural abnormalities (88%). Most frequently observed behavioural problems included autism spectrum disorder (76%), short attention span (32%), abnormal social behaviour (31%), sleep disturbance (29%) and impaired social interactions (28%). Furthermore, abnormalities in the digestive (53%), musculoskeletal (79%) and genitourinary systems (18%) were noted. Although no significant difference in severity was observed between males and females, individuals with a missense variant were less severely affected. Our study provides an exte

Published
2022

31. Loss-of-function variants in SRRM2 cause a neurodevelopmental disorder

Author

Genetica Sectie Genoomdiagnostiek, Child Health, Genetica Klinische Genetica, Circulatory Health, Cuinat, Silvestre, Nizon, Mathilde, Isidor, Bertrand, Stegmann, Alexander, van Jaarsveld, Richard H, van Gassen, Koen L, van der Smagt, Jasper J, Volker-Touw, Catharina M L, Holwerda, Sjoerd J B, Terhal, Paulien A, Schuhmann, Sarah, Vasileiou, Georgia, Khalifa, Mohamed, Nugud, Alaa A, Yasaei, Hemad, Ousager, Lilian Bomme, Brasch-Andersen, Charlotte, Deb, Wallid, Besnard, Thomas, Simon, Marleen E H, Amsterdam, Karin Huijsdens-van, Verbeek, Nienke E, Matalon, Dena, Dykzeul, Natalie, White, Shana, Spiteri, Elizabeth, Devriendt, Koen, Boogaerts, Anneleen, Willemsen, Marjolein, Brunner, Han G, Sinnema, Margje, De Vries, Bert B A, Gerkes, Erica H, Pfundt, Rolph, Izumi, Kosuke, Krantz, Ian D, Xu, Zhou L, Murrell, Jill R, Valenzuela, Irene, Cusco, Ivon, Rovira-Moreno, Eulàlia, Yang, Yaping, Bizaoui, Varoona, Patat, Olivier, Faivre, Laurence, Tran-Mau-Them, Frederic, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Philippe, Christophe, Bezieau, Stéphane, Cogné, Benjamin, Genetica Sectie Genoomdiagnostiek, Child Health, Genetica Klinische Genetica, Circulatory Health, Cuinat, Silvestre, Nizon, Mathilde, Isidor, Bertrand, Stegmann, Alexander, van Jaarsveld, Richard H, van Gassen, Koen L, van der Smagt, Jasper J, Volker-Touw, Catharina M L, Holwerda, Sjoerd J B, Terhal, Paulien A, Schuhmann, Sarah, Vasileiou, Georgia, Khalifa, Mohamed, Nugud, Alaa A, Yasaei, Hemad, Ousager, Lilian Bomme, Brasch-Andersen, Charlotte, Deb, Wallid, Besnard, Thomas, Simon, Marleen E H, Amsterdam, Karin Huijsdens-van, Verbeek, Nienke E, Matalon, Dena, Dykzeul, Natalie, White, Shana, Spiteri, Elizabeth, Devriendt, Koen, Boogaerts, Anneleen, Willemsen, Marjolein, Brunner, Han G, Sinnema, Margje, De Vries, Bert B A, Gerkes, Erica H, Pfundt, Rolph, Izumi, Kosuke, Krantz, Ian D, Xu, Zhou L, Murrell, Jill R, Valenzuela, Irene, Cusco, Ivon, Rovira-Moreno, Eulàlia, Yang, Yaping, Bizaoui, Varoona, Patat, Olivier, Faivre, Laurence, Tran-Mau-Them, Frederic, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Philippe, Christophe, Bezieau, Stéphane, and Cogné, Benjamin

Published
2022

32. Further delineation of auriculocondylar syndrome based on 14 novel cases and reassessment of 25 published cases

Author

Genetica Klinische Genetica, Child Health, Vegas, Nancy, Demir, Zeynep, Gordon, Christopher T, Breton, Sylvain, Romanelli Tavares, Vanessa L, Moisset, Hugo, Zechi-Ceide, Roseli, Kokitsu-Nakata, Nancy M, Kido, Yasuhiro, Marlin, Sandrine, Gherbi Halem, Souad, Meerschaut, Ilse, Callewaert, Bert, Chung, Brian, Revencu, Nicole, Lehalle, Daphné, Petit, Florence, Propst, Evan J, Papsin, Blake C, Phillips, John H, Jakobsen, Linda, Le Tanno, Pauline, Thévenon, Julien, McGaughran, Julie, Gerkes, Erica H, Leoni, Chiara, Kroisel, Peter, Tan, Tiong Y, Henderson, Alex, Terhal, Paulien, Basel-Salmon, Lina, Alkindy, Adila, White, Susan M, Passos-Bueno, Maria R, Pingault, Véronique, De Pontual, Loïc, Amiel, Jeanne, Genetica Klinische Genetica, Child Health, Vegas, Nancy, Demir, Zeynep, Gordon, Christopher T, Breton, Sylvain, Romanelli Tavares, Vanessa L, Moisset, Hugo, Zechi-Ceide, Roseli, Kokitsu-Nakata, Nancy M, Kido, Yasuhiro, Marlin, Sandrine, Gherbi Halem, Souad, Meerschaut, Ilse, Callewaert, Bert, Chung, Brian, Revencu, Nicole, Lehalle, Daphné, Petit, Florence, Propst, Evan J, Papsin, Blake C, Phillips, John H, Jakobsen, Linda, Le Tanno, Pauline, Thévenon, Julien, McGaughran, Julie, Gerkes, Erica H, Leoni, Chiara, Kroisel, Peter, Tan, Tiong Y, Henderson, Alex, Terhal, Paulien, Basel-Salmon, Lina, Alkindy, Adila, White, Susan M, Passos-Bueno, Maria R, Pingault, Véronique, De Pontual, Loïc, and Amiel, Jeanne

Published
2022

33. Further delineation of auriculocondylar syndrome based on 14 novel cases and reassessment of 25 published cases

Author

Vegas, Nancy, primary, Demir, Zeynep, additional, Gordon, Christopher T., additional, Breton, Sylvain, additional, Romanelli Tavares, Vanessa L., additional, Moisset, Hugo, additional, Zechi‐Ceide, Roseli, additional, Kokitsu‐Nakata, Nancy M., additional, Kido, Yasuhiro, additional, Marlin, Sandrine, additional, Gherbi Halem, Souad, additional, Meerschaut, Ilse, additional, Callewaert, Bert, additional, Chung, Brian, additional, Revencu, Nicole, additional, Lehalle, Daphné, additional, Petit, Florence, additional, Propst, Evan J., additional, Papsin, Blake C., additional, Phillips, John H., additional, Jakobsen, Linda, additional, Le Tanno, Pauline, additional, Thévenon, Julien, additional, McGaughran, Julie, additional, Gerkes, Erica H., additional, Leoni, Chiara, additional, Kroisel, Peter, additional, Tan, Tiong Y., additional, Henderson, Alex, additional, Terhal, Paulien, additional, Basel‐Salmon, Lina, additional, Alkindy, Adila, additional, White, Susan M., additional, Passos‐Bueno, Maria R., additional, Pingault, Véronique, additional, De Pontual, Loïc, additional, and Amiel, Jeanne, additional

Published
2022
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34. Familial Multiple Myeloma: Report on Two Families and Discussion of Screening Options

Author

Gerkes Erica H, de Jong Mirjam M, Sijmons Rolf H, and Vellenga Edo

Subjects
multiple myeloma, familial, screening, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Genetics, QH426-470
Abstract

Abstract Multiple myeloma (MM) is a relatively rare haematological malignancy seen in older persons. It has an unknown aetiology and usually occurs incidentally within a family. However, several families have been reported with multiple cases of MM, so that the existence of hereditary MM has been postulated although no causative germline mutations have been detected so far. First-degree relatives of MM patients have been reported to have a relative risk between two and four times higher than normal of developing MM and we presume the risks are higher for relatives in the case of familial MM. Here we report on two families with MM who requested presymptomatic screening of healthy relatives. Although risk estimates for asymptomatic relatives in these types of families are not available, a clinically significant risk of developing MM cannot be excluded. We suggest that, in a research setting, screening for MM could be offered to individuals with more than one first-degree affected relative, or to those with one first-degree and at least one second-degree relative with MM. We propose a screening programme of annual protein electrophoresis of blood and urine, starting at age 40 (or earlier if a family member presented with MM at a younger age).

Published
2007
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35. Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON

Author

Dingemans, Alexander J. M., primary, Truijen, Kim M. G., additional, Kim, Jung-Hyun, additional, Alaçam, Zahide, additional, Faivre, Laurence, additional, Collins, Kathleen M., additional, Gerkes, Erica H., additional, van Haelst, Mieke, additional, van de Laar, Ingrid M. B. H., additional, Lindstrom, Kristin, additional, Nizon, Mathilde, additional, Pauling, James, additional, Heropolitańska-Pliszka, Edyta, additional, Plomp, Astrid S., additional, Racine, Caroline, additional, Sachdev, Rani, additional, Sinnema, Margje, additional, Skranes, Jon, additional, Veenstra-Knol, Hermine E., additional, Verberne, Eline A., additional, Vulto-van Silfhout, Anneke T., additional, Wilsterman, Marlon E. F., additional, Ahn, Eun-Young Erin, additional, de Vries, Bert B. A., additional, and Vissers, Lisenka E. L. M., additional

Published
2021
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36. A Case Series of Familial ARID1B Variants Illustrating Variable Expression and Suggestions to Update the ACMG Criteria

Author

van der Sluijs, Pleuntje J., primary, Alders, Mariëlle, additional, Dingemans, Alexander J. M., additional, Parbhoo, Kareesma, additional, van Bon, Bregje W., additional, Dempsey, Jennifer C., additional, Doherty, Dan, additional, den Dunnen, Johan T., additional, Gerkes, Erica H., additional, Milller, Ilana M., additional, Moortgat, Stephanie, additional, Regier, Debra S., additional, Ruivenkamp, Claudia A. L., additional, Schmalz, Betsy, additional, Smol, Thomas, additional, Stuurman, Kyra E., additional, Vincent-Delorme, Catherine, additional, de Vries, Bert B. A., additional, Sadikovic, Bekim, additional, Hickey, Scott E., additional, Rosenfeld, Jill A., additional, Maystadt, Isabelle, additional, and Santen, Gijs W. E., additional

Published
2021
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37. A case series of familial ARID1B variants illustrating variable expression and suggestions to update the ACMG criteria

Author

van der Sluijs, Pleuntje J., Alders, Mariëlle, Dingemans, Alexander J.M., Parbhoo, Kareesma, van Bon, Bregje W., Dempsey, Jennifer C., Doherty, Dan, Den Dunnen, Johan T., Gerkes, Erica H., Milller, Ilana M., Moortgat, Stephanie, Regier, Debra S., Ruivenkamp, Claudia A.L., Schmalz, Betsy, Smol, Thomas, Stuurman, Kyra E., Vincent-Delorme, Catherine, de Vries, Bert B.A., Sadikovic, Bekim, Hickey, Scott E., Rosenfeld, Jill A., Maystadt, Isabelle, Santen, Gijs W.E., van der Sluijs, Pleuntje J., Alders, Mariëlle, Dingemans, Alexander J.M., Parbhoo, Kareesma, van Bon, Bregje W., Dempsey, Jennifer C., Doherty, Dan, Den Dunnen, Johan T., Gerkes, Erica H., Milller, Ilana M., Moortgat, Stephanie, Regier, Debra S., Ruivenkamp, Claudia A.L., Schmalz, Betsy, Smol, Thomas, Stuurman, Kyra E., Vincent-Delorme, Catherine, de Vries, Bert B.A., Sadikovic, Bekim, Hickey, Scott E., Rosenfeld, Jill A., Maystadt, Isabelle, and Santen, Gijs W.E.

Abstract

ARID1B is one of the most frequently mutated genes in intellectual disability (~1%). Most variants are readily classified, since they are de novo and are predicted to lead to loss of function, and therefore classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines for the interpretation of sequence variants. However, familial loss-of-function variants can also occur and can be challenging to interpret. Such variants may be pathogenic with variable expression, causing only a mild phenotype in a parent. Alternatively, since some regions of the ARID1B gene seem to be lacking pathogenic variants, loss-of-function variants in those regions may not lead to ARID1B haploinsufficiency and may therefore be benign. We describe 12 families with potential loss-of-function variants, which were either familial or with unknown inheritance and were in regions where pathogenic variants have not been described or are otherwise challenging to interpret. We performed detailed clinical and DNA methylation studies, which allowed us to confidently classify most variants. In five families we observed transmission of pathogenic variants, confirming their highly variable expression. Our findings provide further evidence for an alternative translational start site and we suggest updates for the ACMG guidelines for the interpretation of sequence variants to incorporate DNA methylation studies and facial analyses.

Published
2021

39. Mutations in NEK8 link multiple organ dysplasia with altered Hippo signalling and increased c-MYC expression

Author

Frank, Valeska, Habbig, Sandra, Bartram, Malte P., Eisenberger, Tobias, Veenstra-Knol, Hermine E., Decker, Christian, Boorsma, Reinder A.C., Göbel, Heike, Nürnberg, Gudrun, Griessmann, Anabel, Franke, Mareike, Borgal, Lori, Kohli, Priyanka, Völker, Linus A., Dötsch, Jörg, Nürnberg, Peter, Benzing, Thomas, Bolz, Hanno J., Johnson, Colin, Gerkes, Erica H., Schermer, Bernhard, and Bergmann, Carsten

Published
2013
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40. ZMYND11 ‐related syndromic intellectual disability: 16 patients delineating and expanding the phenotypic spectrum

Author

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
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42. The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Author

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

Published
2019

43. Exome sequencing in routine diagnostics: A generic test for 254 patients with primary immunodeficiencies

Author

Haematologie patientenzorg, Infectieziekten patientenzorg, Arts, Peer, Simons, Annet, Alzahrani, Mofareh S., Yilmaz, Elanur, Alidrissi, Eman, Van Aerde, Koen J., Alenezi, Njood, Alghamdi, Hamza A., Aljubab, Hadeel A., Al-Hussaini, Abdulrahman A., Almanjomi, Fahad, Alsaad, Alaa B., Alsaleem, Badr, Andijani, Abdulrahman A., Asery, Ali, Ballourah, Walid, Bleeker-Rovers, Chantal P., Van Deuren, Marcel, Van Der Flier, Michiel, Gerkes, Erica H., Gilissen, Christian, Habazi, Murad K., Hehir-Kwa, Jayne Y., Henriet, Stefanie S., Hoppenreijs, Esther P., Hortillosa, Sarah, Kerkhofs, Chantal H., Keski-Filppula, Riikka, Lelieveld, Stefan H., Lone, Khurram, MacKenzie, Marius A., Mensenkamp, Arjen R., Moilanen, Jukka, Nelen, Marcel, Ten Oever, Jaap, Potjewijd, Judith, Van Paassen, Pieter, Schuurs-Hoeijmakers, Janneke H.M., Simon, Anna, Stokowy, Tomasz, Van De Vorst, Maartje, Vreeburg, Maaike, Wagner, Anja, Van Well, Gijs T.J., Zafeiropoulou, Dimitra, Zonneveld-Huijssoon, Evelien, Veltman, Joris A., Van Zelst-Stams, Wendy A.G., Faqeih, Eissa A., Van De Veerdonk, Frank L., Netea, Mihai G., Hoischen, Alexander, Haematologie patientenzorg, Infectieziekten patientenzorg, Arts, Peer, Simons, Annet, Alzahrani, Mofareh S., Yilmaz, Elanur, Alidrissi, Eman, Van Aerde, Koen J., Alenezi, Njood, Alghamdi, Hamza A., Aljubab, Hadeel A., Al-Hussaini, Abdulrahman A., Almanjomi, Fahad, Alsaad, Alaa B., Alsaleem, Badr, Andijani, Abdulrahman A., Asery, Ali, Ballourah, Walid, Bleeker-Rovers, Chantal P., Van Deuren, Marcel, Van Der Flier, Michiel, Gerkes, Erica H., Gilissen, Christian, Habazi, Murad K., Hehir-Kwa, Jayne Y., Henriet, Stefanie S., Hoppenreijs, Esther P., Hortillosa, Sarah, Kerkhofs, Chantal H., Keski-Filppula, Riikka, Lelieveld, Stefan H., Lone, Khurram, MacKenzie, Marius A., Mensenkamp, Arjen R., Moilanen, Jukka, Nelen, Marcel, Ten Oever, Jaap, Potjewijd, Judith, Van Paassen, Pieter, Schuurs-Hoeijmakers, Janneke H.M., Simon, Anna, Stokowy, Tomasz, Van De Vorst, Maartje, Vreeburg, Maaike, Wagner, Anja, Van Well, Gijs T.J., Zafeiropoulou, Dimitra, Zonneveld-Huijssoon, Evelien, Veltman, Joris A., Van Zelst-Stams, Wendy A.G., Faqeih, Eissa A., Van De Veerdonk, Frank L., Netea, Mihai G., and Hoischen, Alexander

Published
2019

44. The ARID1B spectrum in 143 patients:from nonsyndromic intellectual disability to Coffin–Siris syndrome

Author

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

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. High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Author

Diets, Illja J. Waanders, Esme Ligtenberg, Marjolijn J. van Bladel, Diede A. G. Kamping, Eveline J. Hoogerbrugge, Peter M. and Hopman, Saskia Olderode-Berends, Maran J. Gerkes, Erica H. and Koolen, David A. Marcelis, Carlo Santen, Gijs W. van Belzen, Martine J. Mordaunt, Dylan McGregor, Lesley and Thompson, Elizabeth Kattamis, Antonis Pastorczak, Agata and Mlynarski, Wojciech Ilencikova, Denisa Vulto-van Silfhout, Anneke Gardeitchik, Thatjana de Bont, Eveline S. Loeffen, Jan Wagner, Anja Mensenkamp, Arjen R. Kuiper, Roland P. and Hoogerbrugge, Nicoline Jongmans, Marjolijn C.

Abstract

Purpose: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer. Experimental Design: To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to the whole exome. Results: Four patients carried causative mutations in a known cancer-predisposing gene: TP53 and DICER1 (n = 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (EP300-based Rubinstein-Taybi syndrome, ARID1A-based Coffin-Siris syndrome, ACTB-based Baraitser-Winter syndrome, and EZH2-based Weaver syndrome). In addition, we identified two genes, KDM3B and TYK2, which are possibly involved in genetic cancer predisposition. Conclusions: In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition. (C) 2018 AACR.

Published
2018

47. Variants in nuclear factor I genes influence growth and development

Author

Zenker, Martin, primary, Bunt, Jens, additional, Schanze, Ina, additional, Schanze, Denny, additional, Piper, Michael, additional, Priolo, Manuela, additional, Gerkes, Erica H., additional, Gronostajski, Richard M., additional, Richards, Linda J., additional, Vogt, Julie, additional, Wessels, Marja W., additional, and Hennekam, Raoul C., additional

Published
2019
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48. Improving the diagnostic yield of exome- sequencing by predicting gene–phenotype associations using large-scale gene expression analysis

Author

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

Published
2019
Full Text
View/download PDF

50. High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Author

Diets, Illja J., Waanders, Esme, Ligtenberg, Marjolijn J., van Bladel, Diede A.G., Kamping, Eveline J., Hoogerbrugge, Peter M., Hopman, Saskia, Olderode-Berends, Maran J., Gerkes, Erica H., Koolen, David A., Marcelis, Carlo, Santen, Gijs W., van Belzen, Martine J., Mordaunt, Dylan, McGregor, Lesley, Thompson, Elizabeth, Kattamis, Antonis, Pastorczak, Agata, Mlynarski, Wojciech, Ilencikova, Denisa, Vulto-Van Silfhout, Anneke, Gardeitchik, Thatjana, de Bont, Eveline S., Loeffen, Jan, Wagner, Anja, Mensenkamp, Arjen R., Kuiper, Roland P., Hoogerbrugge, Nicoline, Jongmans, Marjolijn C., Diets, Illja J., Waanders, Esme, Ligtenberg, Marjolijn J., van Bladel, Diede A.G., Kamping, Eveline J., Hoogerbrugge, Peter M., Hopman, Saskia, Olderode-Berends, Maran J., Gerkes, Erica H., Koolen, David A., Marcelis, Carlo, Santen, Gijs W., van Belzen, Martine J., Mordaunt, Dylan, McGregor, Lesley, Thompson, Elizabeth, Kattamis, Antonis, Pastorczak, Agata, Mlynarski, Wojciech, Ilencikova, Denisa, Vulto-Van Silfhout, Anneke, Gardeitchik, Thatjana, de Bont, Eveline S., Loeffen, Jan, Wagner, Anja, Mensenkamp, Arjen R., Kuiper, Roland P., Hoogerbrugge, Nicoline, and Jongmans, Marjolijn C.

Published
2018

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