TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness.

Détails

ID Serval
serval:BIB_14EA38AF16CB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness.
Périodique
American journal of human genetics
Auteur⸱e⸱s
Audo I., Kohl S., Leroy B.P., Munier F.L., Guillonneau X., Mohand-Saïd S., Bujakowska K., Nandrot E.F., Lorenz B., Preising M., Kellner U., Renner A.B., Bernd A., Antonio A., Moskova-Doumanova V., Lancelot M.E., Poloschek C.M., Drumare I., Defoort-Dhellemmes S., Wissinger B., Léveillard T., Hamel C.P., Schorderet D.F., De Baere E., Berger W., Jacobson S.G., Zrenner E., Sahel J.A., Bhattacharya S.S., Zeitz C.
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Statut éditorial
Publié
Date de publication
11/2009
Peer-reviewed
Oui
Volume
85
Numéro
5
Pages
720-729
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Night vision requires signaling from rod photoreceptors to adjacent bipolar cells in the retina. Mutations in the genes NYX and GRM6, expressed in ON bipolar cells, lead to a disruption of the ON bipolar cell response. This dysfunction is present in patients with complete X-linked and autosomal-recessive congenital stationary night blindness (CSNB) and can be assessed by standard full-field electroretinography (ERG), showing severely reduced rod b-wave amplitude and slightly altered cone responses. Although many cases of complete CSNB (cCSNB) are caused by mutations in NYX and GRM6, in approximately 60% of the patients the gene defect remains unknown. Animal models of human diseases are a good source for candidate genes, and we noted that a cCSNB phenotype present in homozygous Appaloosa horses is associated with downregulation of TRPM1. TRPM1, belonging to the family of transient receptor potential channels, is expressed in ON bipolar cells and therefore qualifies as an excellent candidate. Indeed, mutation analysis of 38 patients with CSNB identified ten unrelated cCSNB patients with 14 different mutations in this gene. The mutation spectrum comprises missense, splice-site, deletion, and nonsense mutations. We propose that the cCSNB phenotype in these patients is due to the absence of functional TRPM1 in retinal ON bipolar cells.

Mots-clé
Electroretinography, Female, Genes, Recessive, Heterozygote, Homozygote, Humans, Male, Models, Genetic, Mutation, Night Blindness/congenital, Night Blindness/genetics, Night Blindness/physiopathology, Nuclear Family, Pedigree, TRPM Cation Channels/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/12/2009 11:55
Dernière modification de la notice
20/08/2019 13:43
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