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Numerous BAF complex genes are mutated in Coffin–Siris syndrome
Author(s) -
Miyake Noriko,
Tsurusaki Yoshinori,
Matsumoto Naomichi
Publication year - 2014
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.31406
Subject(s) - smarcb1 , haploinsufficiency , genetics , swi/snf , exome sequencing , mutation , arid1a , intellectual disability , medicine , biology , gene , phenotype , chromatin remodeling , epigenetics
Coffin–Siris syndrome (CSS; OMIM#135900) is a rare congenital anomaly syndrome characterized by intellectual disability, coarse face, hypertrichosis, and absence/hypoplasia of the fifth digits' nails. As the majority of patients are sporadic, an autosomal dominant inheritance model has been postulated. Recently, whole exome sequencing (WES) emerged as a comprehensive analytical method for rare variants. We applied WES on five CSS patients and found two de novo mutations in SMARCB1 . SMARCB1 was completely sequenced in 23 CSS patients and the mutations were found in two more patients. As SMARCB1 encodes a subunit of the BAF complex functioning as a chromatin remodeling factor, mutations in 15 other subunit genes may cause CSS and thus were analyzed in 23 CSS patients. We identified heterozygous mutations in either of six genes ( SMARCA4 , SMARCB1 , SMARCA2 , SMARCE1 , ARID1A , and ARID1B ) in 20 out of 23 CSS patients. The patient with a SMARCA2 mutation was re‐evaluated and identified as having Nicolaides–Baraitser syndrome (OMIM#601358), which is similar to but different from CSS. Additionally, 49 more CSS patients were analyzed as a second cohort. Together with the first cohort, 37 out of 71 (22 plus 49) patients were found to have a mutation in either one of five BAF complex genes. Furthermore, two CSS patients were reported to have a PHF6 abnormality, which can also cause Borjeson–Forssman–Lehmann syndrome (OMIM#301900), an X‐linked intellectual disability syndrome with epilepsy and endocrine abnormalities. The current list of mutated genes in CSS is far from being complete and analysis of more patients is required. © 2014 Wiley Periodicals, Inc.