Mutational screening of splicing factor genes in cases with autosomal dominant retinitis pigmentosa.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_F4712C0BB6F7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mutational screening of splicing factor genes in cases with autosomal dominant retinitis pigmentosa.
Périodique
Molecular Vision
Auteur(s)
Benaglio P., San Jose P.F., Avila-Fernandez A., Ascari G., Harper S., Manes G., Ayuso C., Hamel C., Berson E.L., Rivolta C.
ISSN
1090-0535 (Electronic)
ISSN-L
1090-0535
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
20
Pages
843-851
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Résumé
PURPOSE: Mutations in genes encoding proteins from the tri-snRNP complex of the spliceosome account for more than 12% of cases of autosomal dominant retinitis pigmentosa (adRP). Although the exact mechanism by which splicing factor defects trigger photoreceptor death is not completely clear, their role in retinitis pigmentosa has been demonstrated by several genetic and functional studies. To test for possible novel associations between splicing factors and adRP, we screened four tri-snRNP splicing factor genes (EFTUD2, PRPF4, NHP2L1, and AAR2) as candidate disease genes.
METHODS: We screened up to 303 patients with adRP from Europe and North America who did not carry known RP mutations. Exon-PCR and Sanger methods were used to sequence the NHP2L1 and AAR2 genes, while the sequences of EFTUD2 and PRPF4 were obtained by using long-range PCRs spanning coding and non-coding regions followed by next-generation sequencing.
RESULTS: We detected novel missense changes in individual patients in the sequence of the genes PRPF4 and EFTUD2, but the role of these changes in relationship to disease could not be verified. In one other patient we identified a novel nucleotide substitution in the 5' untranslated region (UTR) of NHP2L1, which did not segregate with the disease in the family.
CONCLUSIONS: The absence of clearly pathogenic mutations in the candidate genes screened in our cohort suggests that EFTUD2, PRPF4, NHP2L1, and AAR2 are either not involved in adRP or are associated with the disease in rare instances, at least as observed in this study in patients of European and North American origin.
Pubmed
Web of science
Création de la notice
05/08/2014 18:51
Dernière modification de la notice
03/03/2018 22:44
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