Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype

Balasubramanian, Meena, Dingemans, Alexander J. M., Albaba, Shadi, Richardson, Ruth, Yates, Thabo M., Cox, Helen, Douzgou, Sofia, Armstrong, Ruth, Sansbury, Francis H., Burke, Katherine B., Fry, Andrew E., 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, Marie, Isidor, Bertrand, Küry, Sebastien, Schouten, Meyke, Leenders, Erika, Chung, Wendy K., Haeringen, Arie van, Scheffner, Thomas, Debray, Francois-Guillaume, White, Susan M., Palafoll, Maria Irene Valenzuela, Pfundt, Rolph, Newbury-Ecob, Ruth and Kleefstra, Tjitske 2021. Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype. European Journal of Human Genetics 29 , pp. 625-636. 10.1038/s41431-020-00769-7

[thumbnail of s41431-020-00769-7.pdf]
PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview


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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Nature Publishing Group
ISSN: 1018-4813
Date of First Compliant Deposit: 7 February 2021
Date of Acceptance: 21 October 2020
Last Modified: 28 Apr 2022 12:29

Citation Data

Cited 4 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics