1. Heterozygous variants in ACTL6A, encoding a component of the BAF complex, are associated with intellectual disability
- Author
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Marom, R., Jain, M., Burrage, L.C., Song, I.W., Graham, B.H., Brown, C.W., Stevens, S.J.C., Stegmann, A.P.A., Gunter, A.T., Kaplan, J.D., Gavrilova, R.H., Shinawi, M., Rosenfeld, J.A., Bae, Y., Tran, A.A., Chen, Y, Lu, J.T., Gibbs, R.A., Eng, C., Yang, Y, Rousseau, J., Vries, B.B.A. de, Campeau, P.M., Lee, B., MUMC+: DA KG Lab Centraal Lab (9), and RS: FHML non-thematic output
- Subjects
Male ,Heterozygote ,speech delay ,Adolescent ,Chromosomal Proteins, Non-Histone ,Micrognathism ,Mutation, Missense ,Article ,CHROMATIN-REMODELING COMPLEX ,Humans ,Exome ,BAF complex ,Child ,HAPLOINSUFFICIENCY CAUSES ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,COFFIN-SIRIS SYNDROME ,DNA Helicases ,Nuclear Proteins ,SWI/SNF COMPLEX ,Chromatin Assembly and Disassembly ,BARAITSER-WINTER SYNDROME ,GENE ,Actins ,NUCLEAR ACTIN ,DNA-Binding Proteins ,ACTIN-RELATED PROTEINS ,intellectual disability ,DE-NOVO MUTATIONS ,Face ,Multiprotein Complexes ,ACTL6A ,Female ,Hand Deformities, Congenital ,MENTAL-RETARDATION ,Protein Binding ,Transcription Factors - Abstract
Item does not contain fulltext 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 beta-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.
- Published
- 2017
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