A loss of function variant in AGPAT3 underlies intellectual disability and retinitis pigmentosa (IDRP) syndrome.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
13
06
2023
accepted:
27
09
2023
revised:
17
08
2023
pmc-release:
01
12
2024
medline:
4
12
2023
pubmed:
12
10
2023
entrez:
11
10
2023
Statut:
ppublish
Résumé
Intellectual disability (ID) and retinal dystrophy (RD) are the frequently found features of multiple syndromes involving additional systemic manifestations. Here, we studied a family with four members presenting severe ID and retinitis pigmentosa (RP). Using genome wide genotyping and exome sequencing, we identified a nonsense variant c.747 C > A (p.Tyr249Ter) in exon 7 of AGPAT3 which co-segregates with the disease phenotype. Western blot analysis of overexpressed WT and mutant AGPAT3 in HEK293T cells showed the absence of AGPAT3, suggesting instability of the truncated protein. Knockdown of Agpat3 in the embryonic mouse brain caused marked deficits in neuronal migration, strongly suggesting that reduced expression of AGPAT3 affects neuronal function. Altogether, our data indicates that AGPAT3 activity is essential for neuronal functioning and loss of its activity probably causes intellectual disability and retinitis pigmentosa (IDRP) syndrome.
Identifiants
pubmed: 37821758
doi: 10.1038/s41431-023-01475-w
pii: 10.1038/s41431-023-01475-w
pmc: PMC10689475
doi:
Substances chimiques
2-acylglycerophosphate acyltransferase
EC 2.3.1.52
Lpaat3 protein, mouse
EC 2.3.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1447-1454Subventions
Organisme : NICHD NIH HHS
ID : R01 HD109342
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD109342
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.
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