Titre

ALDH1A3 loss of function causes bilateral anophthalmia/microphthalmia and hypoplasia of the optic nerve and optic chiasm.

Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Yahyavi, M.
Auteure/Auteur
Abouzeid, H.
Auteure/Auteur
Gawdat, G.
Auteure/Auteur
de Preux, A.S.
Auteure/Auteur
Xiao, T.
Auteure/Auteur
Bardakjian, T.
Auteure/Auteur
Schneider, A.
Auteure/Auteur
Choi, A.
Auteure/Auteur
Jorgenson, E.
Auteure/Auteur
Baier, H.
Auteure/Auteur
El Sada, M.
Auteure/Auteur
Schorderet, D.F.
Auteure/Auteur
Slavotinek, A.M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1460-2083
Statut éditorial
Publié
Date de publication
2013
Volume
22
Numéro
16
Première page
3250
Dernière page/numéro d’article
3258
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Résumé
The major active retinoid, all-trans retinoic acid, has long been recognized as critical for the development of several organs, including the eye. Mutations in STRA6, the gene encoding the cellular receptor for vitamin A, in patients with Matthew-Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated the importance of retinol metabolism in human eye disease. We used homozygosity mapping combined with next-generation sequencing to interrogate patients with anophthalmia and microphthalmia for new causative genes. We used whole-exome and whole-genome sequencing to study a family with two affected brothers with bilateral A/M and a simplex case with bilateral anophthalmia and hypoplasia of the optic nerve and optic chiasm. Analysis of novel sequence variants revealed homozygosity for two nonsense mutations in ALDH1A3, c.568A>G, predicting p.Lys190*, in the familial cases, and c.1165A>T, predicting p.Lys389*, in the simplex case. Both mutations predict nonsense-mediated decay and complete loss of function. We performed antisense morpholino (MO) studies in Danio rerio to characterize the developmental effects of loss of Aldh1a3 function. MO-injected larvae showed a significant reduction in eye size, and aberrant axonal projections to the tectum were noted. We conclude that ALDH1A3 loss of function causes anophthalmia and aberrant eye development in humans and in animal model systems.
PID Serval
serval:BIB_3F2C26782503
DOI
PMID
WOS
Permalien
Open Access
Oui
Date de création
2013-08-13T07:20:56.640Z
Date de création dans IRIS
2025-05-20T15:33:40Z
Fichier(s)
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REF.pdf

Version du manuscrit

published

Taille

400.72 KB

Format

Adobe PDF

PID Serval

serval:BIB_3F2C26782503.P001

URN

urn:nbn:ch:serval-BIB_3F2C267825031

Somme de contrôle

(MD5):20c240273153d10b0f838f43c783898b