Exome sequencing identifies de novo splicing variant in XRCC6 in sporadic case of autism
Autor: | Amy J. M. McNaughton, Melissa Hudson, Calvin Sjaarda, Muhammad Ayub, Sarah M. Taylor, Xudong Liu, Andrea Guerin, Shalandra Wood |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Proband Adult Male DNA Repair RNA Splicing Mutation Missense 030105 genetics & heredity Biology 03 medical and health sciences Neurodevelopmental disorder mental disorders Exome Sequencing Genetics medicine Missense mutation Humans Protein Isoforms Exome Genetic Predisposition to Disease Autistic Disorder Ku Autoantigen Genetics (clinical) Exome sequencing Intron medicine.disease DNA-Binding Proteins 030104 developmental biology Autism spectrum disorder RNA splicing Autism Female RNA Splice Sites Transcription Factors |
Zdroj: | Journal of human genetics. 65(3) |
ISSN: | 1435-232X |
Popis: | Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneity in presentation, genetic etiology, and clinical outcome. Although numerous ASD susceptibility genes have been described, they only account for a small fraction of the estimated heritability, supporting the need to identify more risk variants. This study reports the whole exome sequencing for 24 simplex families with sporadic cases of ASD. These families were selected following a rigorous family history study designed to exclude families with any history of neurodevelopmental or psychiatric disease. Fifteen rare, de novo variants, including fourteen missense variants and one splicing variant, in thirteen families were identified. We describe a splicing variant in XRCC6 which was predicted to destroy the 5' splice site in intron 9 and introduce a premature stop codon. We observed intron 9 retention in XRCC6 transcripts and reduced XRCC6 expression in the proband. Reduced XRCC6 activity and function may be relevant to ASD etiology due to XRCC6's role in nonhomologous DNA repair and interactions of the C-terminal SAP domain with DEAF1, a nuclear transcriptional regulator that is important during embryonic development. |
Databáze: | OpenAIRE |
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