Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome

• Published in: Nature genetics Vol. 44; no. 4; pp. 379 - 380
• Main Authors: Santen, Gijs W E, Aten, Emmelien, Sun, Yu, Almomani, Rowida, Gilissen, Christian, Nielsen, Maartje, Kant, Sarina G, Snoeck, Irina N, Peeters, Els A J, Hilhorst-Hofstee, Yvonne, Wessels, Marja W, den Hollander, Nicolette S, Ruivenkamp, Claudia A L, van Ommen, Gert-Jan B, Breuning, Martijn H, den Dunnen, Johan T, van Haeringen, Arie, Kriek, Marjolein
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2012; Nature Publishing Group
• Subjects: 631/208/176; 631/208/2489/144; 631/208/366; Abnormalities, Multiple - genetics; Agriculture; Analysis; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; brief-communication; Cancer Research; Child; Child, Preschool; Chromatin; Chromatin Assembly and Disassembly - genetics; Coffin-Siris syndrome; Diseases of the osteoarticular system; DNA Copy Number Variations; DNA-Binding Proteins - genetics; Face - abnormalities; Female; Fingers & toes; Fundamental and applied biological sciences. Psychology; Gene Function; Gene mutations; Genes; Genetic aspects; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Genotype & phenotype; Hand Deformities, Congenital - genetics; Human Genetics; Humans; Intellectual Disability - genetics; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Micrognathism - genetics; Middle Aged; Mutation; Neck - abnormalities; Physiological aspects; Sequence Deletion; Speech Disorders - genetics; Transcription Factors - genetics; Netherlands; Gene; Coffin-Siris syndrome; Diseases of the osteoarticular system; Dysostosis; Mutation; Congenital disease; Chromatin remodeling
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2217

Gijs Santen and colleagues report mutations in the SWI/SNF subunit gene ARID1B in Coffin-Siris syndrome. We identified de novo truncating mutations in ARID1B in three individuals with Coffin-Siris syndrome (CSS) by exome sequencing. Array-based copy-number variation (CNV) analysis in 2,000 individuals with intellectual disability revealed deletions encompassing ARID1B in 3 subjects with phenotypes partially overlapping that of CSS. Taken together with published data, these results indicate that haploinsufficiency of the ARID1B gene, which encodes an epigenetic modifier of chromatin structure, is an important cause of CSS and is potentially a common cause of intellectual disability and speech impairment.