title: Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability.
abstract: Intellectual disability (ID) is a clinically and genetically heterogeneous common condition that remains etiologically unresolved in the majority of cases. Although several hundred diseased genes have been identified in X-linked, autosomal-recessive, or syndromic types of ID, the establishment of an etiological basis remains a difficult task in unspecific, sporadic cases. Just recently, de novo mutations in SYNGAP1, STXBP1, MEF2C, and GRIN2B were reported as relatively common causes of ID in such individuals. On the basis of a patient with severe ID and a 2.5 Mb microdeletion including ARID1B in chromosomal region 6q25, we performed mutational analysis in 887 unselected patients with unexplained ID. In this cohort, we found eight (0.9%) additional de novo nonsense or frameshift mutations predicted to cause haploinsufficiency. Our findings indicate that haploinsufficiency of ARID1B, a member of the SWI/SNF-A chromatin-remodeling complex, is a common cause of ID, and they add to the growing evidence that chromatin-remodeling defects are an important contributor to neurodevelopmental disorders.
authors.affiliation: Institute of Human Genetics, University of Erlangen-Nuremberg, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Hoyer
authors.forename: Arif B
authors.initials: AB
authors.lastname: Ekici
authors.forename: Sabine
authors.initials: S
authors.lastname: Endele
authors.forename: Bernt
authors.initials: B
authors.lastname: Popp
authors.forename: Christiane
authors.initials: C
authors.lastname: Zweier
authors.forename: Antje
authors.initials: A
authors.lastname: Wiesener
authors.forename: Eva
authors.initials: E
authors.lastname: Wohlleber
authors.forename: Andreas
authors.initials: A
authors.lastname: Dufke
authors.forename: Eva
authors.initials: E
authors.lastname: Rossier
authors.forename: Corinna
authors.initials: C
authors.lastname: Petsch
authors.forename: Markus
authors.initials: M
authors.lastname: Zweier
authors.forename: Ina
authors.initials: I
authors.lastname: Göhring
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Zink
authors.forename: Gudrun
authors.initials: G
authors.lastname: Rappold
authors.forename: Evelin
authors.initials: E
authors.lastname: Schröck
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Hartmut
authors.initials: H
authors.lastname: Engels
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.forename: André
authors.initials: A
authors.lastname: Reis
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002843:Chromatin / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D057895:Haploinsufficiency; D006801:Humans; D008607:Intellectual Disability; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C497837:ARID1B protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors