Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome

• Published in: Nature genetics Vol. 44; no. 4; pp. 376 - 378
• Main Authors: Tsurusaki, Yoshinori, Okamoto, Nobuhiko, Ohashi, Hirofumi, Kosho, Tomoki, Imai, Yoko, Hibi-Ko, Yumiko, Kaname, Tadashi, Naritomi, Kenji, Kawame, Hiroshi, Wakui, Keiko, Fukushima, Yoshimitsu, Homma, Tomomi, Kato, Mitsuhiro, Hiraki, Yoko, Yamagata, Takanori, Yano, Shoji, Mizuno, Seiji, Sakazume, Satoru, Ishii, Takuma, Nagai, Toshiro, Shiina, Masaaki, Ogata, Kazuhiro, Ohta, Tohru, Niikawa, Norio, Miyatake, Satoko, Okada, Ippei, Mizuguchi, Takeshi, Doi, Hiroshi, Saitsu, Hirotomo, Miyake, Noriko, Matsumoto, Naomichi
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2012; Nature Publishing Group
• Subjects: 631/208/2489/144; 631/208/366; Abnormalities, Multiple - genetics; Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; brief-communication; Cancer Research; Cells, Cultured; Chromatin; Chromosomal Proteins, Non-Histone - genetics; Coffin-Siris syndrome; Diseases of the osteoarticular system; DNA Copy Number Variations - genetics; DNA Helicases - genetics; DNA-Binding Proteins - genetics; Exome; Face - abnormalities; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Gene mutations; Genetic aspects; Genetics; Genetics of eukaryotes. Biological and molecular evolution; 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; Mutation; Mutation, Missense; Neck - abnormalities; Nuclear Proteins - genetics; Physiological aspects; Proteins; Science; Sequence Analysis, DNA; SMARCB1 Protein; Transcription Factors - genetics; Japan; Dysostosis; Mutation; Congenital disease; Coffin-Siris syndrome; Diseases of the osteoarticular system
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2219

Naomichi Matsumoto and colleagues report mutations in the SWI/SNF chromatin remodeling complex in Coffin-Siris syndrome. Twenty affected individuals (87%) harbored mutations in one of six SWI/SNF subunit genes: SMARCB1 , SMARCA4 , SMARCA2 , SMARCE1 , ARID1A or ARID1B . By exome sequencing, we found de novo SMARCB1 mutations in two of five individuals with typical Coffin-Siris syndrome (CSS), a rare autosomal dominant anomaly syndrome. As SMARCB1 encodes a subunit of the SWItch/Sucrose NonFermenting (SWI/SNF) complex, we screened 15 other genes encoding subunits of this complex in 23 individuals with CSS. Twenty affected individuals (87%) each had a germline mutation in one of six SWI/SNF subunit genes, including SMARCB1 , SMARCA4 , SMARCA2 , SMARCE1 , ARID1A and ARID1B .