A family study implicates GBE1 in the etiology of autism spectrum disorder.
autism spectrum disorder
broader autism phenotype
genetics
glycogen branching enzyme
linkage
whole exome sequencing
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
17
09
2021
received:
13
02
2021
accepted:
07
10
2021
pubmed:
12
10
2021
medline:
1
4
2022
entrez:
11
10
2021
Statut:
ppublish
Résumé
Autism spectrum disorders (ASD) are neurodevelopmental disorders with an estimated heritability of >60%. Family-based genetic studies of ASD have generally focused on multiple small kindreds, searching for de novo variants of major effect. We hypothesized that molecular genetic analysis of large multiplex families would enable the identification of variants of milder effects. We studied a large multigenerational family of European ancestry with multiple family members affected with ASD or the broader autism phenotype (BAP). We identified a rare heterozygous variant in the gene encoding 1,4-ɑ-glucan branching enzyme 1 (GBE1) that was present in seven of seven individuals with ASD, nine of ten individuals with the BAP, and none of four tested unaffected individuals. We genotyped a community-acquired cohort of 389 individuals with ASD and identified three additional probands. Cascade analysis demonstrated that the variant was present in 11 of 13 individuals with familial ASD/BAP and neither of the two tested unaffected individuals in these three families, also of European ancestry. The variant was not enriched in the combined UK10K ASD cohorts of European ancestry but heterozygous GBE1 deletion was overrepresented in large ASD cohorts, collectively suggesting an association between GBE1 and ASD.
Identifiants
pubmed: 34633740
doi: 10.1002/humu.24289
pmc: PMC8720068
mid: NIHMS1751077
doi:
Substances chimiques
Glucans
0
Glycogen Debranching Enzyme System
0
1,4-alpha-Glucan Branching Enzyme
EC 2.4.1.18
GBE1 protein, human
EC 2.4.1.18
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16-29Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH101221
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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