Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder.
autism spectrum disorder
copy number variants
nonsense-mediated mRNA decay
single nucleotide variants
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
13 Mar 2022
13 Mar 2022
Historique:
received:
30
11
2021
revised:
04
03
2022
accepted:
07
03
2022
entrez:
25
3
2022
pubmed:
26
3
2022
medline:
26
3
2022
Statut:
epublish
Résumé
Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition with unclear etiology. Many genes have been associated with ASD risk, but the underlying mechanisms are still poorly understood. An important post-transcriptional regulatory mechanism that plays an essential role during neurodevelopment, the Nonsense-Mediated mRNA Decay (NMD) pathway, may contribute to ASD risk. In this study, we gathered a list of 46 NMD factors and regulators and investigated the role of genetic variants in these genes in ASD. By conducting a comprehensive search for Single Nucleotide Variants (SNVs) in NMD genes using Whole Exome Sequencing data from 1828 ASD patients, we identified 270 SNVs predicted to be damaging in 28.7% of the population. We also analyzed Copy Number Variants (CNVs) from two cohorts of ASD patients (N = 3570) and discovered 38 CNVs in 1% of cases. Importantly, we discovered 136 genetic variants (125 SNVs and 11 CNVs) in 258 ASD patients that were located within protein domains required for NMD. These gene variants are classified as damaging using
Identifiants
pubmed: 35327467
pii: biomedicines10030665
doi: 10.3390/biomedicines10030665
pmc: PMC8945030
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Fundação para a Ciência e Tecnologia
ID : PAC-POCI-01-0145-FEDER-016428
Organisme : Fundação para a Ciência e Tecnologia
ID : PD/BD/113773/2015
Organisme : Fundação para a Ciência e Tecnologia
ID : PD/BD/114386/2016
Organisme : Fundação para a Ciência e Tecnologia
ID : UIDB/04046/2020 and UIDP/04046/2020
Organisme : Fundação para a Ciência e Tecnologia
ID : PD/BD/131390/2017
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