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Am J Ophthalmol. 2015 Feb;159(2):302-14. doi: 10.1016/j.ajo.2014.10.033. Epub 2014 Nov 5.

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

Author information

1
Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France. Electronic address: gael.manes@inserm.fr.
2
University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France; CHRU, Genetics of Sensory Diseases, Montpellier, France.
3
The Marie Curie Laboratory for Membrane Proteins, National University of Ireland, Maynooth, Ireland.
4
CHRU Lille, Laboratoire de Biochimie et Biologie Moléculaire, UF Génopathies, Lille, France.
5
Institut National de la Santé et de la Recherche Médicale, U968, Paris, France; Centre National de la Recherche Scientifique, UMR 7210, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, UMR S968, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM, Direction de l'Hospitalisation et de l'Organisation des Soins, Centre d'Investigation Clinique 1423, Paris, France.
6
Institut National de la Santé et de la Recherche Médicale, U968, Paris, France; Centre National de la Recherche Scientifique, UMR 7210, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, UMR S968, Paris, France.
7
Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; CHRU, Genetics of Sensory Diseases, Montpellier, France.
8
Clinique Ophtalmologique Sourdille, Nantes, France.
9
Laboratoire Neurosciences Fonctionnelles et Pathologies, CNRS FRE 2726, Hôpital Roger Salengro, Lille, France.
10
Centre Hospitalier Universitaire de Rennes, Rennes, France.
11
Hôpitaux Universitaires de Strasbourg (HUS), Centre de référence pour les affections rares en génétique ophtalmologique (CARGO), Strasbourg, France.
12
Department of Genetics, INSERM U781, Hôpital Necker Enfants Malades, Université Paris-Descartes, Paris, France.
13
Groupe Hospitalier Necker-Enfants Malades, Université Paris-Descartes, Paris, France.
14
CHU-Hotel Dieu, Service d'Ophtalmologie, Nantes, France.
15
Centre de génétique, hôpital d'Enfants, université de Dijon, Dijon, France.
16
Paris Descartes University, AP-HP Hôtel-Dieu Hospital, Department of Ophthalmology, Paris, France.
17
INSERM UMR_S 910, University of Aix-Marseille, Marseille, France.
18
Clinical Investigation Centre, University Hospital of Montpellier, Montpellier, France.
19
Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; University of Montpellier 1, Montpellier, France.
20
Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France.
21
Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France; CHRU, Genetics of Sensory Diseases, Montpellier, France.
22
CHRU Lille, Laboratoire de Biochimie et Biologie Moléculaire, UF Génopathies, Lille, France; Université Lille Nord de France, Lille, France.

Abstract

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.

PMID:
25447119
DOI:
10.1016/j.ajo.2014.10.033
[Indexed for MEDLINE]
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