Titre
A male with unilateral microphthalmia reveals a role for TMX3 in eye development.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Plos One
Auteur(s)
Chao, R.
Auteure/Auteur
Nevin, L.
Auteure/Auteur
Agarwal, P.
Auteure/Auteur
Riemer, J.
Auteure/Auteur
Bai, X.
Auteure/Auteur
Delaney, A.
Auteure/Auteur
Akana, M.
Auteure/Auteur
JimenezLopez, N.
Auteure/Auteur
Bardakjian, T.
Auteure/Auteur
Schneider, A.
Auteure/Auteur
Chassaing, N.
Auteure/Auteur
Schorderet, D.F.
Auteure/Auteur
FitzPatrick, D.
Auteure/Auteur
Kwok, P.Y.
Auteure/Auteur
Ellgaard, L.
Auteure/Auteur
Gould, D.B.
Auteure/Auteur
Zhang, Y.
Auteure/Auteur
Malicki, J.
Auteure/Auteur
Baier, H.
Auteure/Auteur
Slavotinek, A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1932-6203[electronic], 1932-6203[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
5
Numéro
5
Première page
e10565
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
Anophthalmia and microphthalmia are important birth defects, but their pathogenesis remains incompletely understood. We studied a patient with severe unilateral microphthalmia who had a 2.7 Mb deletion at chromosome 18q22.1 that was inherited from his mother. In-situ hybridization showed that one of the deleted genes, TMX3, was expressed in the retinal neuroepithelium and lens epithelium in the developing murine eye. We re-sequenced TMX3 in 162 patients with anophthalmia or microphthalmia, and found two missense substitutions in unrelated patients: c.116G>A, predicting p.Arg39Gln, in a male with unilateral microphthalmia and retinal coloboma, and c.322G>A, predicting p.Asp108Asn, in a female with unilateral microphthalmia and severe micrognathia. We used two antisense morpholinos targeted against the zebrafish TMX3 orthologue, zgc:110025, to examine the effects of reduced gene expression in eye development. We noted that the morphant larvae resulting from both morpholinos had significantly smaller eye sizes and reduced labeling with islet-1 antibody directed against retinal ganglion cells at 2 days post fertilization. Co-injection of human wild type TMX3 mRNA rescued the small eye phenotype obtained with both morpholinos, whereas co-injection of human TMX3(p.Arg39Gln) mutant mRNA, analogous to the mutation in the patient with microphthalmia and coloboma, did not rescue the small eye phenotype. Our results show that haploinsufficiency for TMX3 results in a small eye phenotype and represents a novel genetic cause of microphthalmia and coloboma. Future experiments to determine if other thioredoxins are important in eye morphogenesis and to clarify the mechanism of function of TMX3 in eye development are warranted.
Sujets
PID Serval
serval:BIB_41E9F009D72C
PMID
Open Access
Oui
Date de création
2010-10-14T07:08:11.819Z
Date de création dans IRIS
2025-05-20T14:00:55Z
Fichier(s)![Vignette d'image]()
En cours de chargement...
Nom
BIB_41E9F009D72C.P001.pdf
Version du manuscrit
preprint
Taille
2.45 MB
Format
Adobe PDF
PID Serval
serval:BIB_41E9F009D72C.P001
URN
urn:nbn:ch:serval-BIB_41E9F009D72C1
Somme de contrôle
(MD5):9f9d0ddb67f1d9c45edbf67f110c8898