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504 results on '"Gillessen-Kaesbach G"'

2. Humangenetik

Author

Gillessen-Kaesbach, G., Hellenbroich, Y., Speer, Christian P., editor, Gahr, Manfred, editor, and Dötsch, Jörg, editor

Published
2019
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4. Humangenetik

Author

Gillessen-Kaesbach, G., Hellenbroich, Y., Speer, Christian P., editor, and Gahr, Manfred, editor

Published
2013
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6. Humangenetik

Author

Gillessen-Kaesbach, G., Kulozik, A. E., Speer, Christian P., and Gahr, Manfred

Published
2009
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8. Expanding the clinical spectrum of the ‘HDAC8-phenotype’ – implications for molecular diagnostics, counseling and risk prediction

Author

Parenti, I., Gervasini, C., Pozojevic, J., Wendt, K. S., Watrin, E., Azzollini, J., Braunholz, D., Buiting, K., Cereda, A., Engels, H., Garavelli, L., Glazar, R., Graffmann, B., Larizza, L., Lüdecke, H. J., Mariani, M., Masciadri, M., Pié, J., Ramos, F. J., Russo, S., Selicorni, A., Stefanova, M., Strom, T. M., Werner, R., Wierzba, J., Zampino, G., Gillessen-Kaesbach, G., Wieczorek, D., and Kaiser, F. J.

Published
2016
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9. X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

Author

Hu, H, Haas, S A, Chelly, J, Van Esch, H, Raynaud, M, de Brouwer, A PM, Weinert, S, Froyen, G, Frints, S GM, Laumonnier, F, Zemojtel, T, Love, M I, Richard, H, Emde, A-K, Bienek, M, Jensen, C, Hambrock, M, Fischer, U, Langnick, C, Feldkamp, M, Wissink-Lindhout, W, Lebrun, N, Castelnau, L, Rucci, J, Montjean, R, Dorseuil, O, Billuart, P, Stuhlmann, T, Shaw, M, Corbett, M A, Gardner, A, Willis-Owen, S, Tan, C, Friend, K L, Belet, S, van Roozendaal, K EP, Jimenez-Pocquet, M, Moizard, M-P, Ronce, N, Sun, R, OʼKeeffe, S, Chenna, R, van Bömmel, A, Göke, J, Hackett, A, Field, M, Christie, L, Boyle, J, Haan, E, Nelson, J, Turner, G, Baynam, G, Gillessen-Kaesbach, G, Müller, U, Steinberger, D, Budny, B, Badura-Stronka, M, Latos-Bieleńska, A, Ousager, L B, Wieacker, P, Criado, G Rodríguez, Bondeson, M-L, Annerén, G, Dufke, A, Cohen, M, Van Maldergem, L, Vincent-Delorme, C, Echenne, B, Simon-Bouy, B, Kleefstra, T, Willemsen, M, Fryns, J-P, Devriendt, K, Ullmann, R, Vingron, M, Wrogemann, K, Wienker, T F, Tzschach, A, van Bokhoven, H, Gecz, J, Jentsch, T J, Chen, W, Ropers, H-H, and Kalscheuer, V M

Published
2016
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12. Array-CGH: Erfahrungen aus Schleswig-Holstein

Author

Caliebe, A., Platzer, K., Argyriou, L., Bens, S., Hellenbroich, Y., Husemeyer, N., Nagel, I., Martin-Subero, J.I., Sporns, P., Stefanova, I., Tönnies, H., Vater, I., Weimer, J., Siebert, R., and Gillessen-Kaesbach, G.

Published
2012
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23. Development, behaviour and autism in individuals with SMC1A variants

Author

Mulder, P.A., Huisman, S., Landlust, A.M., Moss, J., Bader, I., Balkom, I.D.C. van, Bisgaard, A.M., Brooks, A., Cereda, A., Cinca, C., Clark, D., Cormier-Daire, V., Deardorff, M.A., Diderich, K., Elting, M., Essen, A. van, FitzPatrick, D., Gervasini, C., Gillessen-Kaesbach, G., Girisha, K.M., Hennekam, R.C., Hilhorst-Hofstee, Y., Hopman, S., Horn, D., Isrie, M., Jansen, S., Jespersgaard, C., Kaiser, F.J., Kaur, M., Kleefstra, T., Krantz, I.D., Lakeman, P., Lessel, D., Michot, C., Noon, S.E., Oliver, C., Parenti, I., Pie, J., Piening, S., Puisac, B., Ramos, F.J., Redeker, E., Rieubland, C., Russo, S., Selicorni, A., Tumer, Z., Vorstenbosch, R., Vries, I.M., Wenger, T.L., Wierzba, J., SMC1A Consortium, Clinical Genetics, Pediatric surgery, APH - Quality of Care, Human genetics, Amsterdam Reproduction & Development (AR&D), Graduate School, ANS - Cellular & Molecular Mechanisms, and Paediatric Genetics

Subjects
cognition, Male, Autism Spectrum Disorder, Chromosomal Proteins, Non-Histone, CHILDREN, Cell Cycle Proteins, COMMUNICATION, Pediatrics, 0302 clinical medicine, De Lange Syndrome, Intellectual disability, Developmental and Educational Psychology, Spectrum disorder, Child, self-injurious behaviour, 05 social sciences, SELF-INJURIOUS-BEHAVIOR, Perinatology, PREVALENCE, and Child Health, Psychiatry and Mental health, Phenotype, DE-LANGE-SYNDROME, Autism spectrum disorder, Child, Preschool, Female, Psychology, 050104 developmental & child psychology, Clinical psychology, Behavioural phenotype, Adult, Down syndrome, cornelia de lange syndrome, Cornelia de Lange Syndrome, Adolescent, autism, Rett syndrome, 03 medical and health sciences, Young Adult, All institutes and research themes of the Radboud University Medical Center, Journal Article, medicine, Humans, 0501 psychology and cognitive sciences, Cognitive Dysfunction, Pediatrics, Perinatology, and Child Health, rett syndrome, SPECTRUM DISORDER, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], MUTATIONS, Infant, NIPBL, medicine.disease, Cross-Sectional Studies, Pediatrics, Perinatology and Child Health, Autism, Down Syndrome, Self-Injurious Behavior, 030217 neurology & neurosurgery
Abstract

Introduction: Development and behaviour in Cornelia de Lange Syndrome (CdLS), including autism characteristics, have been described infrequently stratified to genetic cause and only a few studies have considered behavioural characteristics in relation to developmental level. Here, we describe the behavioural phenotype in individuals with CdLS with SMC1A variants. Methods: We performed an international, interdisciplinary study on 51 individuals with SMC1A variants. Results of questionnaire studies are compared to those in individuals with Down Syndrome and with Autism Spectrum Disorder. Results on cognition and self-injurious behaviour (SIB) are compared to those in individuals with CdLS caused by NIPBL variants. For Dutch participants with SMC1A variants we performed direct in-person assessments of cognition, autism, and added an interview and questionnaire on adaptive behaviour and sensory processing. Results: Individuals with SMC1A variants show a higher cognitive level and less SIB than individuals with NIPBL variants. Individuals with SMC1A variants without classic CdLS phenotype but with a Rett-like phenotype show more severe intellectual disability and more SIB compared to those with a CdLS phenotype. Autism is less present if outcomes in direct in-person assessments are evaluated taking developmental level into account compared to results based on a questionnaire. Conclusions: Behaviour in individuals with CdLS should be evaluated taking genetic cause into account. Detailed interdisciplinary approaches are of clinical importance to inform tailored care and may eventually improve quality of life of patients and families.

Published
2019
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28. Arterial Tortuosity Syndrome: Clinical and Molecular Findings in 12 Newly Identified Families

Author

Callewaert, B. L., Willaert, A., Kerstjens-Frederikse, W. S., De Backer, J., Devriendt, K., Albrecht, B., Ramos-Arroyo, M. A., Doco-Fenzy, M., Hennekam, R. C.M., Pyeritz, R. E., Krogmann, O. N., Gillessen-kaesbach, G., Wakeling, E. L., Nik-zainal, S., Francannet, C., Mauran, P., Booth, C., Barrow, M., Dekens, R., Loeys, B. L., Coucke, P. J., and De Paepe, A. M.

Published
2008
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30. The adult phenotype of Schaaf-Yang syndrome

Author

Marbach, F., Elgizouli, M., Rech, M., Beygo, J., Erger, F., Velmans, C., Stumpel, C. T. R. M., Stegmann, A. P. A., Beck-Woedl, S., Gillessen-Kaesbach, G., Horsthemke, B., Schaaf, C. P., Kuechler, A., Marbach, F., Elgizouli, M., Rech, M., Beygo, J., Erger, F., Velmans, C., Stumpel, C. T. R. M., Stegmann, A. P. A., Beck-Woedl, S., Gillessen-Kaesbach, G., Horsthemke, B., Schaaf, C. P., and Kuechler, A.

Published
2020

33. Novel gene and pathomechanism in Cornelia de Lange syndrome

Author

Parenti, I., Ruiz Gil, S., Pie, J., Strom, T. M., Brouwer, R., Diab, F., Dupe, V., Gillessen-Kaesbach, G., Mulugeta, E., Ijcken, W., Ramos, F., erwan watrin, Wendt, K. S., Kaiser, F. J., Universität zu Lübeck [Lübeck], University of Zaragoza - Universidad de Zaragoza [Zaragoza], Helmholtz-Zentrum München (HZM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Universität zu Lübeck = University of Lübeck [Lübeck], Helmholtz Zentrum München = German Research Center for Environmental Health, and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

36. Genotypic and Phenotypic Spectrum in Tricho-Rhino-Phalangeal Syndrome Types I and III

Author

Lüdecke, H.-J., Schaper, J., Meinecke, P., Momeni, P., Groß, S., von Holtum, D., Hirche, H., Abramowicz, M.J., Albrecht, B., Apacik, C., Christen, H.-J., Claussen, U., Devriendt, K., Fastnacht, E., Forderer, A., Friedrich, U., Goodship, T.H.J., Greiwe, M., Hamm, H., Hennekam, R.C.M., Hinkel, G.K., Hoeltzenbein, M., Kayserili, H., Majewski, F., Mathieu, M., McLeod, R., Midro, A.T., Moog, U., Nagai, T., Niikawa, N., Ørstavik, K.H., Plöchl, E., Seitz, C., Schmidtke, J., Tranebjærg, L., Tsukahara, M., Wittwer, B., Zabel, B., Gillessen-Kaesbach, G., and Horsthemke, B.

Published
2001
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40. Molecular and clinical studies in 8 patients with Temple syndrome

Author

Gillessen‐Kaesbach, G., primary, Albrecht, B., additional, Eggermann, T., additional, Elbracht, M., additional, Mitter, D., additional, Morlot, S., additional, van Ravenswaaij‐Arts, C.M.A., additional, Schulz, S., additional, Strobl‐Wildemann, G., additional, Buiting, K., additional, and Beygo, J., additional

Published
2018
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41. The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

Author

Koolen, D.A., Pfundt, R., Linda, K., Beunders, G., Veenstra-Knol, H.E., Conta, J.H., Fortuna, A.M., Gillessen-Kaesbach, G., Dugan, S., Halbach, S., Abdul-Rahman, O.A., Winesett, H.M., Chung, W.K., Dalton, M., Dimova, P.S., Mattina, T., Prescott, K., Zhang, H.Z., Saal, H.M., Hehir-Kwa, J.Y., Willemsen, M.H., Ockeloen, C.W., Jongmans, M.C., Aa, N. van der, Failla, P., Barone, C., Avola, E., Brooks, A.S., Kant, S.G., Gerkes, E.H., Firth, H.V., Ounap, K., Bird, L.M., Masser-Frye, D., Friedman, J.R., Sokunbi, M.A., Dixit, A., Splitt, M., Kukolich, M.K., McGaughran, J., Coe, B.P., Florez, J., Kasri, N.N., Brunner, H.G., Thompson, E.M., Gecz, J., Romano, C., Eichler, E.E., Vries, B.B.A. de, DDD Study, Clinical Genetics, Klinische Genetica, MUMC+: DA Klinische Genetica (5), Genetica & Celbiologie, RS: FHML non-thematic output, RS: GROW - School for Oncology and Reproduction, RS: GROW - R4 - Reproductive and Perinatal Medicine, and DDD Study

Subjects
0301 basic medicine, Male, Congenital, Epilepsy, Intellectual disability, MAPT, 2.1 Biological and endogenous factors, Koolen-de Vries syndrome, KANSL1, phenotype, Genetics(clinical), Copy-number variation, Aetiology, Non-U.S. Gov't, Child, Genetics (clinical), Pediatric, Genetics & Heredity, Genetics, COMMON INVERSION, DEVELOPMENTAL DELAY, Research Support, Non-U.S. Gov't, Nuclear Proteins, Single Nucleotide, Microdeletion syndrome, Middle Aged, Hypotonia, Chemistry, DROSOPHILA, Phenotype, Female, Abnormalities, medicine.symptom, Chromosome Deletion, Haploinsufficiency, Multiple, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Human, Adult, Adolescent, Koolen De Vries syndrome, INVERSION POLYMORPHISM, Intellectual and Developmental Disabilities (IDD), Clinical Sciences, Copy number analysis, COPY-NUMBER VARIATION, Biology, Research Support, Polymorphism, Single Nucleotide, Chromosomes, Article, 03 medical and health sciences, Rare Diseases, Clinical Research, Intellectual Disability, Journal Article, medicine, Humans, Abnormalities, Multiple, Polymorphism, DDD Study, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], COMPLEX, MUTATIONS, Pair 17, DISABILITY, Neurosciences, medicine.disease, Brain Disorders, DELINEATION, 030104 developmental biology, Congenital Structural Anomalies, Human medicine, Chromosomes, Human, Pair 17
Abstract

Contains fulltext : 168191.pdf (Publisher’s version ) (Open Access) 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

42. Mutations in Multidomain Protein MEGF8 Identify a Carpenter Syndrome Subtype Associated with Defective Lateralization

Author

Twigg, SR, Lloyd, D, Jenkins, D, Elçioglu, NE, Cooper, CD, Al-Sannaa, N, Annagür, A, Gillessen-Kaesbach, G, Hüning, I, Knight, SJ, Goodship, JA, Keavney, BD, Beales, PL, Gileadi, O, McGowan, SJ, and Wilkie, AO

Subjects
QH301, Genetics, Genetics(clinical)
Abstract

Carpenter syndrome is an autosomal-recessive multiple-congenital- malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor- like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed. © 2012 The American Society of Human Genetics.

Published
2012
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43. Phenotypes and genotypes in individuals with SMC1A variants

Author

Huisman, S., Mulder, P.A., Redeker, E., Bader, I., Bisgaard, A.M., Brooks, A., Cereda, A., Cinca, C., Clark, D., Cormier-Daire, V., Deardorff, M.A., Diderich, K., Elting, M., Essen, A. van, Fitzpatrick, D., Gervasini, C., Gillessen-Kaesbach, G., Girisha, K.M., Hilhorst-Hofstee, Y., Hopman, S., Horn, D., Isrie, M., Jansen, S, Jespersgaard, C., Kaiser, F.J., Kaur, M., Kleefstra, T., Krantz, I.D., Lakeman, P., Landlust, A., Lessel, D., Michot, C., Moss, J., Noon, S.E., Oliver, C., Parenti, I., Pie, J., Ramos, F.J., Rieubland, C., Russo, S., Selicorni, A., Tumer, Z., Vorstenbosch, R., Wenger, T.L., Balkom, I.D.C. van, Piening, S., Wierzba, J., Hennekam, R.C., Huisman, S., Mulder, P.A., Redeker, E., Bader, I., Bisgaard, A.M., Brooks, A., Cereda, A., Cinca, C., Clark, D., Cormier-Daire, V., Deardorff, M.A., Diderich, K., Elting, M., Essen, A. van, Fitzpatrick, D., Gervasini, C., Gillessen-Kaesbach, G., Girisha, K.M., Hilhorst-Hofstee, Y., Hopman, S., Horn, D., Isrie, M., Jansen, S, Jespersgaard, C., Kaiser, F.J., Kaur, M., Kleefstra, T., Krantz, I.D., Lakeman, P., Landlust, A., Lessel, D., Michot, C., Moss, J., Noon, S.E., Oliver, C., Parenti, I., Pie, J., Ramos, F.J., Rieubland, C., Russo, S., Selicorni, A., Tumer, Z., Vorstenbosch, R., Wenger, T.L., Balkom, I.D.C. van, Piening, S., Wierzba, J., and Hennekam, R.C.

Abstract

Item does not contain fulltext, SMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed an international, interdisciplinary study on 51 individuals with SMC1A variants for physical and behavioral characteristics, and compare results to those in 67 individuals with NIPBL variants. For the Netherlands all known individuals with SMC1A variants were studied, both with and without CdLS phenotype. Individuals with SMC1A variants can resemble CdLS, but manifestations are less marked compared to individuals with NIPBL variants: growth is less disturbed, facial signs are less marked (except for periocular signs and thin upper vermillion), there are no major limb anomalies, and they have a higher level of cognitive and adaptive functioning. Self-injurious behavior is more frequent and more severe in the NIPBL group. In the Dutch group 5 of 13 individuals (all females) had a phenotype that shows a remarkable resemblance to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group suggest that a disturbed cohesin function contributes to the phenotype, but differences between these groups may also be explained by other underlying mechanisms such as moonlighting of the cohesin genes.

Published
2017

44. Phenotypes and genotypes in individuals with SMC1A variants

Author

Huisman, S.A. (Sylvia), Mulder, P.A. (Paul A.), Redeker, E.J.W. (Egbert), Bader, I. (Ingrid), Bisgaard, A.-M. (Anne-Marie), Brooks, A.S. (Alice), Cereda, A., Cinca, C. (Constanza), Clark, D. (Dinah), Cormier-Daire, V. (Valerie), Deardorff, M.A. (Matthew), Diderich, K.E.M. (Karin), Elting, M. (Mariet), Essen, J.A. (Anthonie) van, Fitzpatrick, D.R. (David R.), Gervasini, C., Gillessen-Kaesbach, G. (Gabriele), Girisha, K.M. (Katta M), Hilhorst-Hofstee, Y. (Yvonne), Hopman, S.M.J. (Saskia), Horn, D. (Denise), Isrie, M. (Mala), Jansen, S. (Sandra), Jespersgaard, C. (Cathrine), Kaiser, F.J. (Frank), Kaur, M. (Maninder), Kleefstra, T. (Tjitske), Krantz, D.H. (David), Lakeman, P. (Phillis), Landlust, A. (Annemiek), Lessel, D. (Davor), Michot, C. (Caroline), Moss, J. (Jo), Noon, S.E. (Sarah E.), Oliver, C. (Chris), Parenti, I., Pie, J. (Juan), Ramos, F.J., Rieubland, C. (Claudine), Russo, S. (Sascha), Selicorni, A. (Angelo), Tümer, Z., Vorstenbosch, R. (Rieneke), Wenger, T.L. (Tara L.), van Balkom, I. (Ingrid), Piening, S. (Sigrid), Wierzba, J. (Jolanta), Hennekam, R.C.M. (Raoul), Huisman, S.A. (Sylvia), Mulder, P.A. (Paul A.), Redeker, E.J.W. (Egbert), Bader, I. (Ingrid), Bisgaard, A.-M. (Anne-Marie), Brooks, A.S. (Alice), Cereda, A., Cinca, C. (Constanza), Clark, D. (Dinah), Cormier-Daire, V. (Valerie), Deardorff, M.A. (Matthew), Diderich, K.E.M. (Karin), Elting, M. (Mariet), Essen, J.A. (Anthonie) van, Fitzpatrick, D.R. (David R.), Gervasini, C., Gillessen-Kaesbach, G. (Gabriele), Girisha, K.M. (Katta M), Hilhorst-Hofstee, Y. (Yvonne), Hopman, S.M.J. (Saskia), Horn, D. (Denise), Isrie, M. (Mala), Jansen, S. (Sandra), Jespersgaard, C. (Cathrine), Kaiser, F.J. (Frank), Kaur, M. (Maninder), Kleefstra, T. (Tjitske), Krantz, D.H. (David), Lakeman, P. (Phillis), Landlust, A. (Annemiek), Lessel, D. (Davor), Michot, C. (Caroline), Moss, J. (Jo), Noon, S.E. (Sarah E.), Oliver, C. (Chris), Parenti, I., Pie, J. (Juan), Ramos, F.J., Rieubland, C. (Claudine), Russo, S. (Sascha), Selicorni, A. (Angelo), Tümer, Z., Vorstenbosch, R. (Rieneke), Wenger, T.L. (Tara L.), van Balkom, I. (Ingrid), Piening, S. (Sigrid), Wierzba, J. (Jolanta), and Hennekam, R.C.M. (Raoul)

Abstract

SMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed an international, interdisciplinary study on 51 individuals with SMC1A variants for physical and behavioral characteristics, and compare results to those in 67 individuals with NIPBL variants. For the Netherlands all known individuals with SMC1A variants were studied, both with and without CdLS phenotype. Individuals with SMC1A variants can resemble CdLS, but manifestations are less marked compared to individuals with NIPBL variants: growth is less disturbed, facial signs are less marked (except for periocular signs and thin upper vermillion), there are no major limb anomalies, and they have a higher level of cognitive and adaptive functioning. Self-injurious behavior is more frequent and more severe in the NIPBL group. In the Dutch group 5 of 13 individuals (all females) had a phenotype that shows a remarkable resemblance to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group suggest that a disturbed cohesin function contributes to the phenotype, but differences between these groups may also be explained by other underlying mechanisms such as moonlighting of the cohesin genes.

Published
2017
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45. Phenotypes and genotypes in individuals with SMC1A variants

Author

Huisman, S, Mulder, PA, Redeker, E, Bader, I, Bisgaard, AM, Brooks, A, Cereda, A, Cinca, C, Clark, D, Cormier-Daire, V, Deardorff, MA, Diderich, K, Elting, M, van Essen, A, FitzPatrick, D, Gervasini, C, Gillessen-Kaesbach, G, Girisha, KM, Hilhorst-Hofstee, Y, Hopman, S, Horn, D, Isrie, M, Jansen, S (Silke), Jespersgaard, C, Kaiser, FJ, Kaur, M, Kleefstra, T, Krantz, ID, Lakeman, P, Landlust, A, Lessel, D, Michot, C, Moss, J, Noon, SE, Oliver, C, Parenti, I, Pie, J, Ramos, FJ, Rieubland, C, Russo, S, Selicorni, A, Tumer, Z, van de Vorstenbosch, R, Wenger, TL, van Balkom, I, Piening, S, Wierzba, J, Hennekam, RC, Huisman, S, Mulder, PA, Redeker, E, Bader, I, Bisgaard, AM, Brooks, A, Cereda, A, Cinca, C, Clark, D, Cormier-Daire, V, Deardorff, MA, Diderich, K, Elting, M, van Essen, A, FitzPatrick, D, Gervasini, C, Gillessen-Kaesbach, G, Girisha, KM, Hilhorst-Hofstee, Y, Hopman, S, Horn, D, Isrie, M, Jansen, S (Silke), Jespersgaard, C, Kaiser, FJ, Kaur, M, Kleefstra, T, Krantz, ID, Lakeman, P, Landlust, A, Lessel, D, Michot, C, Moss, J, Noon, SE, Oliver, C, Parenti, I, Pie, J, Ramos, FJ, Rieubland, C, Russo, S, Selicorni, A, Tumer, Z, van de Vorstenbosch, R, Wenger, TL, van Balkom, I, Piening, S, Wierzba, J, and Hennekam, RC

Published
2017

46. Mutational Spectrum in the [Delta]7-Sterol Reductase Gene and Genotype-Phenotype Correlation in 84 Patients with Smith-Lemli-Opitz Syndrome

Author

Witsch-Baumgartner, M., Fitzky, B. U., Ogorelkova, M., Kraft, H. G., Moebius, F. F., Glossmann, H., Seedorf, U., Gillessen-Kaesbach, G., Hoffmann, G. F., Clayton, P., Kelley, R. I., and Utermann, G.

Subjects
Gene mutations -- Analysis, Cholesterol -- Genetic aspects, Sterols -- Physiological aspects, Clinical biochemistry -- Research, Biological sciences
Published
2000

47. X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

Author

Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., Richard, H., Emde, A-K, Bienek, M., Jensen, C., Hambrock, M., Fischer, U., Langnick, C., Feldkamp, M., Wissink-Lindhout, W., Lebrun, N., Castelnau, L., Rucci, J., Montjean, R., Dorseuil, O., Billuart, P., Stuhlmann, T., Shaw, M., Corbett, M. A., Gardner, A., Willis-Owen, S., Tan, C., Friend, K. L., Belet, S., van Roozendaal, K. E. P., Jimenez-Pocquet, M., Moizard, M-P, Ronce, N., Sun, R., O'Keeffe, S., Chenna, R., Van Boemmel, A., Goeke, J., Hackett, A., Field, M., Christie, L., Boyle, J., Haan, E., Nelson, J., Turner, G., Baynam, G., Gillessen-Kaesbach, G., Mueller, U., Steinberger, D., Budny, B., Badura-Stronka, M., Latos-Bielenska, A., Ousager, L. B., Wieacker, P., Criado, G. Rodriguez, Bondeson, Marie-Louise, Annerén, Göran, Dufke, A., Cohen, M., Van Maldergem, L., Vincent-Delorme, C., Echenne, B., Simon-Bouy, B., Kleefstra, T., Willemsen, M., Fryns, J-P, Devriendt, K., Ullmann, R., Vingron, M., Wrogemann, K., Wienker, T. F., Tzschach, A., van Bokhoven, H., Gecz, J., Jentsch, T. J., Chen, W., Ropers, H-H, Kalscheuer, V. M., Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., Richard, H., Emde, A-K, Bienek, M., Jensen, C., Hambrock, M., Fischer, U., Langnick, C., Feldkamp, M., Wissink-Lindhout, W., Lebrun, N., Castelnau, L., Rucci, J., Montjean, R., Dorseuil, O., Billuart, P., Stuhlmann, T., Shaw, M., Corbett, M. A., Gardner, A., Willis-Owen, S., Tan, C., Friend, K. L., Belet, S., van Roozendaal, K. E. P., Jimenez-Pocquet, M., Moizard, M-P, Ronce, N., Sun, R., O'Keeffe, S., Chenna, R., Van Boemmel, A., Goeke, J., Hackett, A., Field, M., Christie, L., Boyle, J., Haan, E., Nelson, J., Turner, G., Baynam, G., Gillessen-Kaesbach, G., Mueller, U., Steinberger, D., Budny, B., Badura-Stronka, M., Latos-Bielenska, A., Ousager, L. B., Wieacker, P., Criado, G. Rodriguez, Bondeson, Marie-Louise, Annerén, Göran, Dufke, A., Cohen, M., Van Maldergem, L., Vincent-Delorme, C., Echenne, B., Simon-Bouy, B., Kleefstra, T., Willemsen, M., Fryns, J-P, Devriendt, K., Ullmann, R., Vingron, M., Wrogemann, K., Wienker, T. F., Tzschach, A., van Bokhoven, H., Gecz, J., Jentsch, T. J., Chen, W., Ropers, H-H, and Kalscheuer, V. M.

Abstract

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.

Published
2016
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48. Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes: A challenge for molecular analysis and genetic counseling.

Author

Prawitt D., Begemann M., Soellner L., Eggermann K., Tenorio J., Nevado J., Moore G.E., Mackay D.J.G., Temple K., Gillessen-Kaesbach G., Ogata T., Weksberg R., Algar E., Lapunzina P., Eggermann T., Brioude F., Russo S., Lombardi M.P., Bliek J., Maher E.R., Larizza L., Netchine I., Gonzales M., Gronskov K., Tumer Z., Monk D., Mannens M., Chrzanowska K., Walasek M.K., Prawitt D., Begemann M., Soellner L., Eggermann K., Tenorio J., Nevado J., Moore G.E., Mackay D.J.G., Temple K., Gillessen-Kaesbach G., Ogata T., Weksberg R., Algar E., Lapunzina P., Eggermann T., Brioude F., Russo S., Lombardi M.P., Bliek J., Maher E.R., Larizza L., Netchine I., Gonzales M., Gronskov K., Tumer Z., Monk D., Mannens M., Chrzanowska K., and Walasek M.K.

Abstract

Beckwith-Wiedemann and Silver-Russell syndromes (BWS/SRS) are two imprinting disorders (IDs) associated with disturbances of the 11p15.5 chromosomal region. In BWS, epimutations and genomic alterations within 11p15.5 are observed in >70% of patients, whereas in SRS they are observed in about 60% of the cases. In addition, 10% of the SRS patients carry a maternal uniparental disomy of chromosome 7 11p15.5. There is an increasing demand for prenatal testing of these disorders owing to family history, indicative prenatal ultrasound findings or aberrations involving chromosomes 7 and 11. The complex molecular findings underlying these disorders are a challenge not only for laboratories offering these tests but also for geneticists counseling affected families. The scope of counseling must consider the range of detectable disturbances and their origin, the lack of precise quantitative knowledge concerning the inheritance and recurrence risks for the epigenetic abnormalities, which are hallmarks of these developmental disorders. In this paper, experts in the field of BWS and SRS, including members of the European network of congenital IDs (EUCID.net; www.imprinting-disorders.eu), put together their experience and work in the field of 11p15.5-Associated IDs with a focus on prenatal testing. Altogether, prenatal tests of 160 fetuses (122 referred for BWS, 38 for SRS testing) from 5 centers were analyzed and reviewed. We summarize the current knowledge on BWS and SRS with respect to diagnostic testing, the consequences for prenatal genetic testing and counseling and our cumulative experience in dealing with these disorders.Copyright © 2016 Macmillan Publishers Limited.

Published
2016

50. Dysmorphology at a distance: results of a web-based diagnostic service

Author

Douzgou, S, Clayton-Smith, J, Gardner, S, Day, R, Griffiths, P, Strong, K, Amiel, J, Baraitser, M, Brueton, L, Brunner, H, Chrzanowska, K, Dallapiccola, B, Del Campo Casanelles, M, Devriendt, K, Donnai, D, Fitzpatrick, D, Gillessen-Kaesbach, G, Houge, G, Kerr, B, Krajewska-Walasek, M, Lacombe, D, Meinecke, P, Metcalfe, K, Mortier, G, Odent, S, Philip, N, Prescott, T, Raas-Rothschild, A, Rauch, A, Rittinger, O, Salonen, R, Schrander-Stumpel, C, Suri, M, Temple, K, Tolmie, J, Van Der Burgt, I, Verloes, A, Wieczorek, D, Zenker, M, University of Zurich, and Douzgou, S

Subjects
2716 Genetics (clinical), 1311 Genetics, 10039 Institute of Medical Genetics, 570 Life sciences, biology, 610 Medicine & health
Published
2014

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