title: Coffin-Siris syndrome and related disorders involving components of the BAF (mSWI/SNF) complex: historical review and recent advances using next generation sequencing.
abstract: This issue of Seminars in Medical Genetics, American Journal of Medical Genetics Part C investigates the human diseases caused by mutations in the BAF complex (also known as the mammalian SWI/SNF complex) genes, particularly focusing on Coffin-Siris syndrome (CSS). CSS is a rare congenital malformation syndrome characterized by developmental delay or intellectual disability (ID), coarse facial appearance, feeding difficulties, frequent infections, and hypoplasia/aplasia of the fifth fingernails and fifth distal phalanges. In 2012, 42 years after the first description of CSS in 1970, five causative genes (SMARCB1, SMARCE1, SMARCA4, ARID1A, ARID1B), all encoding components of the BAF complex, were identified as being responsible for CSS through whole exome sequencing and pathway-based genetic screening. The identification of two additional causative genes (PHF6, SOX11) followed. Mutations in another BAF complex gene (SMARCA2) and (TBC1D24) were found to cause clinically similar conditions with ID, Nicolaides-Baraitser syndrome and DOORS syndrome, respectively. Also, ADNP was found to be mutated in an autism/ID syndrome. Furthermore, there is growing evidences for germline or somatic mutations in the BAF complex genes to be causal for cancer/cancer predisposition syndromes. These discoveries have highlighted the role of the BAF complex in the human development and cancer formation. The biology of BAF is very complicated and much remains unknown. Ongoing research is required to reveal the whole picture of the BAF complex in human development, and will lead to the development of new targeted therapies for related disorders in the future.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosho
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: John C
authors.initials: JC
authors.lastname: Carey
mesh_terms: D000015:Abnormalities, Multiple / Q000209:etiology* / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006228:Hand Deformities, Congenital / Q000209:etiology* / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology* / Q000235:genetics; D008844:Micrognathism / Q000209:etiology* / Q000235:genetics; D009333:Neck / Q000002:abnormalities*; D009369:Neoplasms / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D000071796:SMARCB1 Protein; 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