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

Abstract

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.

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Figure 1: Photographs of individuals with Coffin-Siris syndrome.

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Acknowledgements

We thank all the family members for participating in this study. This work was supported by research grants from the Ministry of Health, Labour and Welfare (to N. Miyake, H.S. and N. Matsumoto), the Japan Science and Technology Agency (to N. Matsumoto), the Strategic Research Program for Brain Sciences (to N. Matsumoto), the Japan Epilepsy Research Foundation (to H.S.) and the Takeda Science Foundation (to N. Matsumoto and N. Miyake). This study was also funded by a Grant-in-Aid for Scientific Research on Innovative Areas (Foundation of Synapse and Neurocircuit Pathology) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to N. Matsumoto), a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to N. Matsumoto), a Grant-in-Aid for Young Scientists from the Japan Society for the Promotion of Science (to N. Miyake and H.S.) and a Grant for 2011 Strategic Research Promotion of Yokohama City University (to N. Matsumoto). This study was performed at the Advanced Medical Research Center at Yokohama City University. Informed consent was obtained from all the families of affected individuals. The Institutional Review Board of Yokohama City University approved this study.

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Y.T., S. Miyatake, I.O., H.D., H.S. and N. Miyake performed exome sequencing and Sanger sequencing. Y.T., M.S., K.O., I.O., T.M., H.D., H.S. and N. Miyake performed data management and analysis. N.O., H.O., T. Kosho, Y.I., Y.H.-K., T. Kaname, K.N., H.K., K.W., Y.F., T.H., M.K., Y.H., T.Y., S.Y., S. Mizuno, S.S., T.I., T.N., T.O. and N.N. provided clinical materials after careful evaluation. Y.T., N. Miyake and N. Matsumoto wrote the manuscript. N. Matsumoto designed and oversaw all aspects of the study.

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Correspondence to Noriko Miyake or Naomichi Matsumoto.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Figures 1–8 and Supplementary Tables 1–3 (PDF 6781 kb)

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Tsurusaki, Y., Okamoto, N., Ohashi, H. et al. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet 44, 376–378 (2012). https://doi.org/10.1038/ng.2219

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