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Heterozygous variants in ACTL6A , encoding a component of the BAF complex, are associated with intellectual disability
Author(s) -
Marom Ronit,
Jain Mahim,
Burrage Lindsay C.,
Song IWen,
Graham Brett H.,
Brown Chester W.,
Stevens Servi J.C.,
Stegmann Alexander P.A.,
Gunter Andrew T.,
Kaplan Julie D.,
Gavrilova Ralitza H.,
Shinawi Marwan,
Rosenfeld Jill A.,
Bae Yangjin,
Tran Alyssa A.,
Chen Yuqing,
Lu James T.,
Gibbs Richard A.,
Eng Christine,
Yang Yaping,
Rousseau Justine,
Vries Bert B.A.,
Campeau Philippe M.,
Lee Brendan
Publication year - 2017
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23282
Subject(s) - biology , missense mutation , intellectual disability , genetics , rna splicing , gene , mutation , chromatin remodeling , chromatin , rna
Pathogenic variants in genes encoding components of the BRG1‐associated factor (BAF) chromatin remodeling complex have been associated with intellectual disability syndromes. We identified heterozygous, novel variants in ACTL6A , a gene encoding a component of the BAF complex, in three subjects with varying degrees of intellectual disability. Two subjects have missense variants affecting highly conserved amino acid residues within the actin‐like domain. Missense mutations in the homologous region in yeast actin were previously reported to be dominant lethal and were associated with impaired binding of the human ACTL6A to β‐actin and BRG1. A third subject has a splicing variant that creates an in‐frame deletion. Our findings suggest that the variants identified in our subjects may have a deleterious effect on the function of the protein by disturbing the integrity of the BAF complex. Thus, ACTL6A gene mutation analysis should be considered in patients with intellectual disability, learning disabilities, or developmental language disorder.