Where are the missing gene defects in inherited retinal disorders? Intronic and synonymous variants contribute at least to 4% of CACNA1F-mediated inherited retinal disorders.

Détails

ID Serval
serval:BIB_E45B22185DFD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Where are the missing gene defects in inherited retinal disorders? Intronic and synonymous variants contribute at least to 4% of CACNA1F-mediated inherited retinal disorders.
Périodique
Human mutation
Auteur(s)
Zeitz C., Michiels C., Neuillé M., Friedburg C., Condroyer C., Boyard F., Antonio A., Bouzidi N., Milicevic D., Veaux R., Tourville A., Zoumba A., Seneina I., Foussard M., Andrieu C., N Preising M., Blanchard S., Saraiva J.P., Mesrob L., Le Floch E., Jubin C., Meyer V., Blanché H., Boland A., Deleuze J.F., Sharon D., Drumare I., Defoort-Dhellemmes S., De Baere E., Leroy B.P., Zanlonghi X., Casteels I., de Ravel T.J., Balikova I., K Koenekoop R., Laffargue F., McLean R., Gottlob I., Bonneau D., Schorderet D.F., L Munier F., McKibbin M., Prescott K., Pelletier V., Dollfus H., Perdomo-Trujillo Y., Faure C., Reiff C., Wissinger B., Meunier I., Kohl S., Banin E., Zrenner E., Jurklies B., Lorenz B., Sahel J.A., Audo I.
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Statut éditorial
Publié
Date de publication
06/2019
Peer-reviewed
Oui
Volume
40
Numéro
6
Pages
765-787
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Inherited retinal disorders (IRD) represent clinically and genetically heterogeneous diseases. To date, pathogenic variants have been identified in ~260 genes. Albeit that many genes are implicated in IRD, for 30-50% of the cases, the gene defect is unknown. These cases may be explained by novel gene defects, by overlooked structural variants, by variants in intronic, promoter or more distant regulatory regions, and represent synonymous variants of known genes contributing to the dysfunction of the respective proteins. Patients with one subgroup of IRD, namely incomplete congenital stationary night blindness (icCSNB), show a very specific phenotype. The major cause of this condition is the presence of a hemizygous pathogenic variant in CACNA1F. A comprehensive study applying direct Sanger sequencing of the gene-coding regions, exome and genome sequencing applied to a large cohort of patients with a clinical diagnosis of icCSNB revealed indeed that seven of the 189 CACNA1F-related cases have intronic and synonymous disease-causing variants leading to missplicing as validated by minigene approaches. These findings highlight that gene-locus sequencing may be a very efficient method in detecting disease-causing variants in clinically well-characterized patients with a diagnosis of IRD, like icCSNB.
Mots-clé
CACNA1F, IRD, gene defect, icCSNB, intronic variants, minigene approach, synonymous variants
Pubmed
Web of science
Création de la notice
24/06/2019 9:53
Dernière modification de la notice
20/08/2019 16:07
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