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Hum Mutat. 2017 Oct;38(10):1365-1371. doi: 10.1002/humu.23282. Epub 2017 Jul 10.

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

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
2
Department of Pediatrics/Genetics Division, University of Tennessee Health Science Center Memphis, Memphis, Tennessee.
3
Department of Human Genetics, Maastricht University Hospital, Maastricht, The Netherlands.
4
Department of Pediatrics, Division of Medical Genetics, University of Mississippi Medical Center, Jackson, Mississippi.
5
Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota.
6
Department of Neurology, Mayo Clinic, Rochester, Minnesota.
7
Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, Missouri.
8
Helix, San Carlos, California.
9
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
10
Department of Pediatrics, CHU Ste-Justine and University of Montreal, Montreal, Canada.
11
Department of Human Genetics and Donders Centre for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.

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.

KEYWORDS:

ACTL6A; BAF complex; intellectual disability; speech delay

PMID:
28649782
PMCID:
PMC5599325
DOI:
10.1002/humu.23282
[Indexed for MEDLINE]
Free PMC Article

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