Identification of two novel autism genes, TRPC4 and SCFD2, in Qatar simplex families through exome sequencing
This study investigated the genetic underpinnings of autism spectrum disorder (ASD) in a Middle Eastern cohort in Qatar using exome sequencing. The study identified six candidate autism genes in independent simplex families, including both four known and two novel autosomal dominant and autosomal re...
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Published in | Frontiers in psychiatry Vol. 14; p. 1251884 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
31.10.2023
|
Subjects | |
Online Access | Get full text |
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Summary: | This study investigated the genetic underpinnings of autism spectrum disorder (ASD) in a Middle Eastern cohort in Qatar using exome sequencing. The study identified six candidate autism genes in independent simplex families, including both four known and two novel autosomal dominant and autosomal recessive genes associated with ASD. The variants consisted primarily of
de novo
and homozygous missense and splice variants. Multiple individuals displayed more than one candidate variant, suggesting the potential involvement of digenic or oligogenic models. These variants were absent in the Genome Aggregation Database (gnomAD) and exhibited extremely low frequencies in the local control population dataset. Two novel autism genes,
TRPC4
and
SCFD2
, were discovered in two Qatari autism individuals. Furthermore, the D651A substitution in
CLCN3
and the splice acceptor variant in
DHX30
were identified as likely deleterious mutations. Protein modeling was utilized to evaluate the potential impact of three missense variants in
DEAF1
,
CLCN3
, and
SCFD2
on their respective structures and functions, which strongly supported the pathogenic natures of these variants. The presence of multiple
de novo
mutations across trios underscored the significant contribution of
de novo
mutations to the genetic etiology of ASD. Functional assays and further investigations are necessary to confirm the pathogenicity of the identified genes and determine their significance in ASD. Overall, this study sheds light on the genetic factors underlying ASD in Qatar and highlights the importance of considering diverse populations in ASD research. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1664-0640 1664-0640 |
DOI: | 10.3389/fpsyt.2023.1251884 |