dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Balasubramanian, Meena |
dc.contributor.author | Dingemans, Alexander J. M. |
dc.contributor.author | Albaba, Shadi |
dc.contributor.author | Richardson, Ruth |
dc.contributor.author | Yates, Thabo M. |
dc.contributor.author | Cox, Helen |
dc.contributor.author | Valenzuela Palafoll, Ma Irene |
dc.date.accessioned | 2022-02-22T07:25:45Z |
dc.date.available | 2022-02-22T07:25:45Z |
dc.date.issued | 2021-04 |
dc.identifier.citation | Balasubramanian M, Dingemans AJM, Albaba S, Richardson R, Yates TM, Cox H, et al. Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype. Eur J Hum Genet. 2021 Apr;29:625–636. |
dc.identifier.issn | 1476-5438 |
dc.identifier.uri | https://hdl.handle.net/11351/7051 |
dc.description | Autism spectrum disorders; Genetic testing |
dc.description.abstract | Witteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10–12. |
dc.language.iso | eng |
dc.publisher | Springer Nature |
dc.relation.ispartofseries | European Journal of Human Genetics;29 |
dc.rights | Attribution 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.source | Scientia |
dc.subject | Infants |
dc.subject | Trastorns del desenvolupament - Aspectes genètics |
dc.subject | Fenotip |
dc.subject.mesh | Developmental Disabilities |
dc.subject.mesh | /genetics |
dc.subject.mesh | Child |
dc.subject.mesh | Phenotype |
dc.title | Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1038/s41431-020-00769-7 |
dc.subject.decs | discapacidades del desarrollo |
dc.subject.decs | /genética |
dc.subject.decs | niño |
dc.subject.decs | fenotipo |
dc.relation.publishversion | https://doi.org/10.1038/s41431-020-00769-7 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut Català de la Salut |
dc.contributor.authoraffiliation | [Balasubramanian M] Sheffield Clinical Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK. Academic Unit of Child Health, Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK. [Dingemans AJM] Department of Human Genetics, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands. [Albaba S] Sheffield Diagnostic Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK. [Richardson R] Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Trust, Newcastle, UK. [Yates TM] Sheffield Clinical Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK. [Cox H] West Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham Women’s and Children’s Hospitals NHS Foundation Trust, Birmingham, UK. [Palafoll MIV] Servei de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Medicina Genètica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain |
dc.identifier.pmid | 33437032 |
dc.identifier.wos | 000607321000003 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |