Heterozygous variants in ACTL6A, encoding a component of the BAF complex, are associated with intellectual disability.

TitleHeterozygous variants in ACTL6A, encoding a component of the BAF complex, are associated with intellectual disability.
Publication TypeJournal Article
Year of Publication2017
AuthorsMarom, R, Jain, M, Burrage, LC, Song, I-W, Graham, BH, Brown, CW, Stevens, SJC, Stegmann, APA, Gunter, AT, Kaplan, JD, Gavrilova, RH, Shinawi, M, Rosenfeld, JA, Bae, Y, Tran, AA, Chen, Y, Lu, JT, Gibbs, RA, Eng, C, Yang, Y, Rousseau, J, de Vries, BBA, Campeau, PM, Lee, B
JournalHum Mutat
Volume38
Issue10
Pagination1365-1371
Date Published2017 Oct
ISSN1098-1004
Abstract

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.

DOI10.1002/humu.23282
Alternate JournalHum. Mutat.
PubMed ID28649782
PubMed Central IDPMC5599325
Grant ListK08 DK106453 / DK / NIDDK NIH HHS / United States
U54 HG006542 / HG / NHGRI NIH HHS / United States
T32 GM007526 / GM / NIGMS NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P30 HD024064 / HD / NICHD NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
P30 AI036211 / AI / NIAID NIH HHS / United States
S10 RR024574 / RR / NCRR NIH HHS / United States
P01 HD070394 / HD / NICHD NIH HHS / United States