High prevalence of PRPH2 in autosomal dominant retinitis pigmentosa in france and characterization of biochemical and clinical features.

Détails

Ressource 1Télécharger: BIB_E9379337ECE2.P001.pdf (2029.76 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_E9379337ECE2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
High prevalence of PRPH2 in autosomal dominant retinitis pigmentosa in france and characterization of biochemical and clinical features.
Périodique
American Journal of Ophthalmology
Auteur(s)
Manes G., Guillaumie T., Vos W.L., Devos A., Audo I., Zeitz C., Marquette V., Zanlonghi X., Defoort-Dhellemmes S., Puech B., Said S.M., Sahel J.A., Odent S., Dollfus H., Kaplan J., Dufier J.L., Le Meur G., Weber M., Faivre L., Behar-Cohen F., Béroud C., Picot M.C., Verdier C., Sénéchal A., Baudoin C., Bocquet B., Findlay J.B., Meunier I., Dhaenens C.M., Hamel C.P.
ISSN
1879-1891 (Electronic)
ISSN-L
0002-9394
Statut éditorial
Publié
Date de publication
02/2015
Peer-reviewed
Oui
Volume
159
Numéro
2
Pages
302-314
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
PURPOSE: To assess the prevalence of PRPH2 in autosomal dominant retinitis pigmentosa (adRP), to report 6 novel mutations, to characterize the biochemical features of a recurrent novel mutation, and to study the clinical features of adRP patients.
DESIGN: Retrospective clinical and molecular genetic study.
METHODS: Clinical investigations included visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, and electroretinogram (ERG) recording. PRPH2 was screened by Sanger sequencing in a cohort of 310 French families with adRP. Peripherin-2 protein was produced in yeast and analyzed by Western blot.
RESULTS: We identified 15 mutations, including 6 novel and 9 previously reported changes in 32 families, accounting for a prevalence of 10.3% in this adRP population. We showed that a new recurrent p.Leu254Gln mutation leads to protein aggregation, suggesting abnormal folding. The clinical severity of the disease in examined patients was moderate with 78% of the eyes having 1-0.5 of visual acuity and 52% of the eyes retaining more than 50% of the visual field. Some patients characteristically showed vitelliform deposits or macular involvement. In some families, pericentral RP or macular dystrophy were found in family members while widespread RP was present in other members of the same families.
CONCLUSIONS: The mutations in PRPH2 account for 10.3% of adRP in the French population, which is higher than previously reported (0%-8%) This makes PRPH2 the second most frequent adRP gene after RHO in our series. PRPH2 mutations cause highly variable phenotypes and moderate forms of adRP, including mild cases, which could be underdiagnosed.
Mots-clé
Adolescent, Adult, Aged, Blotting, Western, DNA Mutational Analysis, Electroretinography, Female, Fluorescein Angiography, France/epidemiology, Gene Expression, Genetic Linkage, Genotype, Humans, Male, Microsatellite Repeats, Middle Aged, Molecular Biology, Mutation, Pedigree, Peripherins/genetics, Prevalence, Retinitis Pigmentosa/diagnosis, Retinitis Pigmentosa/epidemiology, Retrospective Studies, Tomography, Optical Coherence, Visual Field Tests
Pubmed
Web of science
Création de la notice
01/02/2016 18:05
Dernière modification de la notice
20/08/2019 17:11
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