Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype
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Published:2021-01-12
Issue:4
Volume:29
Page:625-636
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ISSN:1018-4813
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Container-title:European Journal of Human Genetics
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language:en
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Short-container-title:Eur J Hum Genet
Author:
Balasubramanian Meena, Dingemans Alexander J. M., Albaba Shadi, Richardson Ruth, Yates Thabo M.ORCID, Cox Helen, Douzgou Sofia, Armstrong Ruth, Sansbury Francis H.ORCID, Burke Katherine B., Fry Andrew E.ORCID, Ragge Nicola, Sharif Saba, Foster Alison, De Sandre-Giovannoli Annachiara, Elouej Sahar, Vasudevan Pradeep, Mansour Sahar, Wilson Kate, Stewart Helen, Heide Solveig, Nava Caroline, Keren Boris, Demirdas Serwet, Brooks Alice S., Vincent MarieORCID, Isidor Bertrand, Küry SebastienORCID, Schouten Meyke, Leenders Erika, Chung Wendy K., Haeringen Arie van, Scheffner Thomas, Debray Francois-Guillaume, White Susan M.ORCID, Palafoll Maria Irene ValenzuelaORCID, Pfundt Rolph, Newbury-Ecob Ruth, Kleefstra Tjitske
Abstract
AbstractWitteveen-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.
Publisher
Springer Science and Business Media LLC
Subject
Genetics(clinical),Genetics
Reference16 articles.
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