title: Clinical correlations of mutations affecting six components of the SWI/SNF complex: detailed description of 21 patients and a review of the literature.
abstract: Mutations in the components of the SWItch/sucrose nonfermentable (SWI/SNF)-like chromatin remodeling complex have recently been reported to cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and ARID1B-related intellectual disability (ID) syndrome. We detail here the genotype-phenotype correlations for 85 previously published and one additional patient with mutations in the SWI/SNF complex: four with SMARCB1 mutations, seven with SMARCA4 mutations, 37 with SMARCA2 mutations, one with an SMARCE1 mutation, three with ARID1A mutations, and 33 with ARID1B mutations. The mutations were associated with syndromic ID and speech impairment (severe/profound in SMARCB1, SMARCE1, and ARID1A mutations; variable in SMARCA4, SMARCA2, and ARID1B mutations), which was frequently accompanied by agenesis or hypoplasia of the corpus callosum. SMARCB1 mutations caused "classical" CSS with typical facial "coarseness" and significant digital/nail hypoplasia. SMARCA4 mutations caused CSS without typical facial coarseness and with significant digital/nail hypoplasia. SMARCA2 mutations caused NCBRS, typically with short stature, sparse hair, a thin vermillion of the upper lip, an everted lower lip and prominent finger joints. A SMARCE1 mutation caused CSS without typical facial coarseness and with significant digital/nail hypoplasia. ARID1A mutations caused the most severe CSS with severe physical complications. ARID1B mutations caused CSS without typical facial coarseness and with mild digital/nail hypoplasia, or caused syndromic ID. Because of the common underlying mechanism and overlapping clinical features, we propose that these conditions be referred to collectively as "SWI/SNF-related ID syndromes".
authors: Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan. ktomoki@shinshuu.ac.jp
authors: Tomoki
authors: T
authors: Kosho
authors: Nobuhiko
authors: N
authors: Okamoto
authors: Hirofumi
authors: H
authors: Ohashi
authors: Yoshinori
authors: Y
authors: Tsurusaki
authors: Yoko
authors: Y
authors: Imai
authors: Yumiko
authors: Y
authors: Hibi-Ko
authors: Hiroshi
authors: H
authors: Kawame
authors: Tomomi
authors: T
authors: Homma
authors: Saori
authors: S
authors: Tanabe
authors: Mitsuhiro
authors: M
authors: Kato
authors: Yoko
authors: Y
authors: Hiraki
authors: Takanori
authors: T
authors: Yamagata
authors: Shoji
authors: S
authors: Yano
authors: Satoru
authors: S
authors: Sakazume
authors: Takuma
authors: T
authors: Ishii
authors: Toshiro
authors: T
authors: Nagai
authors: Tohru
authors: T
authors: Ohta
authors: Norio
authors: N
authors: Niikawa
authors: Seiji
authors: S
authors: Mizuno
authors: Tadashi
authors: T
authors: Kaname
authors: Kenji
authors: K
authors: Naritomi
authors: Yoko
authors: Y
authors: Narumi
authors: Keiko
authors: K
authors: Wakui
authors: Yoshimitsu
authors: Y
authors: Fukushima
authors: Satoko
authors: S
authors: Miyatake
authors: Takeshi
authors: T
authors: Mizuguchi
authors: Hirotomo
authors: H
authors: Saitsu
authors: Noriko
authors: N
authors: Miyake
authors: Naomichi
authors: N
authors: Matsumoto
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D019066:Facies; D005260:Female; D005532:Foot Deformities, Congenital / Q000235:genetics*; D056726:Genetic Association Studies; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics*; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008844:Micrognathism / Q000235:genetics*; D009154:Mutation; D009333:Neck / Q000002:abnormalities*; D009687:Nuclear Proteins / Q000235:genetics; D000071796:SMARCB1 Protein; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C112476:ARID1A protein, human; C497837:ARID1B protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C084011:SMARCA2 protein, human; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C504738:SMARCE1 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases