The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant
| Autor: | 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 |
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| Přispěvatelé: | 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, DDD Study |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
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 |
| Zdroj: | European Journal of Human Genetics, 24(5), 652-659 European Journal of Human Genetics, 24(5), 652-659. Nature Publishing Group European Journal of Human Genetics, 24, 652-9 European Journal of Human Genetics, 24(5), 652. Nature Publishing Group European journal of human genetics : EJHG, vol 24, iss 5 European Journal of Human Genetics, 24, 5, pp. 652-9 European journal of human genetics |
| ISSN: | 1018-4813 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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