TY - JOUR
T1 - Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort
AU - Ben-Mahmoud, Afif
AU - Gupta, Vijay
AU - Abdelaleem, Alice
AU - Thompson, Richard
AU - Aden, Abdi
AU - Mbarek, Hamdi
AU - Saad, Chadi
AU - Tolefat, Mohamed
AU - Alshaban, Fouad
AU - Stanton, Lawrence W.
AU - Kim, Hyung Goo
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/11
Y1 - 2024/11
N2 - Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Despite considerable research efforts, the genetic complexity of ASD remains poorly understood, complicating diagnosis and treatment, especially in the Arab population, with its genetic diversity linked to migration, tribal structures, and high consanguinity. To address the scarcity of ASD genetic data in the Middle East, we conducted genome sequencing (GS) on 50 ASD subjects and their unaffected parents. Our analysis revealed 37 single-nucleotide variants from 36 candidate genes and over 200 CGG repeats in the FMR1 gene in one subject. The identified variants were classified as uncertain, likely pathogenic, or pathogenic based on in-silico algorithms and ACMG criteria. Notably, 52% of the identified variants were homozygous, indicating a recessive genetic architecture to ASD in this population. This finding underscores the significant impact of high consanguinity within the Qatari population, which could be utilized in genetic counseling/screening program in Qatar. We also discovered single nucleotide variants in 13 novel genes not previously associated with ASD: ARSF, BAHD1, CHST7, CUL2, FRMPD3, KCNC4, LFNG, RGS4, RNF133, SCRN2, SLC12A8, USP24, and ZNF746. Our investigation categorized the candidate genes into seven groups, highlighting their roles in cognitive development, including the ubiquitin pathway, transcription factors, solute carriers, kinases, glutamate receptors, chromatin remodelers, and ion channels.
AB - Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Despite considerable research efforts, the genetic complexity of ASD remains poorly understood, complicating diagnosis and treatment, especially in the Arab population, with its genetic diversity linked to migration, tribal structures, and high consanguinity. To address the scarcity of ASD genetic data in the Middle East, we conducted genome sequencing (GS) on 50 ASD subjects and their unaffected parents. Our analysis revealed 37 single-nucleotide variants from 36 candidate genes and over 200 CGG repeats in the FMR1 gene in one subject. The identified variants were classified as uncertain, likely pathogenic, or pathogenic based on in-silico algorithms and ACMG criteria. Notably, 52% of the identified variants were homozygous, indicating a recessive genetic architecture to ASD in this population. This finding underscores the significant impact of high consanguinity within the Qatari population, which could be utilized in genetic counseling/screening program in Qatar. We also discovered single nucleotide variants in 13 novel genes not previously associated with ASD: ARSF, BAHD1, CHST7, CUL2, FRMPD3, KCNC4, LFNG, RGS4, RNF133, SCRN2, SLC12A8, USP24, and ZNF746. Our investigation categorized the candidate genes into seven groups, highlighting their roles in cognitive development, including the ubiquitin pathway, transcription factors, solute carriers, kinases, glutamate receptors, chromatin remodelers, and ion channels.
KW - Qatari cohort
KW - autism spectrum disorder
KW - genome sequencing
KW - molecular pathways
KW - novel genes
UR - http://www.scopus.com/inward/record.url?scp=85208542752&partnerID=8YFLogxK
U2 - 10.3390/ijms252111551
DO - 10.3390/ijms252111551
M3 - Article
AN - SCOPUS:85208542752
SN - 1661-6596
VL - 25
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 21
M1 - 11551
ER -