June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Screening of PRPH2/RDS in patients with autosomal dominant retinitis pigmentosa reveals novel disease-causing mutations and 8.6% prevalence in French population
Author Affiliations & Notes
  • Gael Manes
    U1051, INSERM, Montpellier, France
  • Claire-Marie Dhaenens
    Laboratoire de génétique moléculaire, Centre Hospitalier Universitaire de Lille, Lille, France
  • Werner Vos
    National University of Ireland, Maynooth, Ireland
  • Isabelle Audo
    Service d’ophtalmologie, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France
  • Xavier Zanlonghi
    Clinique Sourdille, Nantes, France
  • Sylvie Odent
    Service de génétique clinique, Centre Hospitalier Universitaire de Rennes, Rennes, France
  • Helene Dollfus
    Centre de référence national pour les Affections Rares en Génétique Ophtalmologique, Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France
  • Beatrice Bocquet
    Centre de référence maladies rares (Maolya), Centre Hospitalier Universitaire de Montpellier, Montpellier, France
  • Isabelle Meunier
    Centre de référence maladies rares (Maolya), Centre Hospitalier Universitaire de Montpellier, Montpellier, France
  • Christian Hamel
    U1051, INSERM, Montpellier, France
    Centre de référence maladies rares (Maolya), Centre Hospitalier Universitaire de Montpellier, Montpellier, France
  • Footnotes
    Commercial Relationships Gael Manes, None; Claire-Marie Dhaenens, None; Werner Vos, None; Isabelle Audo, None; Xavier Zanlonghi, None; Sylvie Odent, None; Helene Dollfus, None; Beatrice Bocquet, None; Isabelle Meunier, None; Christian Hamel, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 659. doi:
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      Gael Manes, Claire-Marie Dhaenens, Werner Vos, Isabelle Audo, Xavier Zanlonghi, Sylvie Odent, Helene Dollfus, Beatrice Bocquet, Isabelle Meunier, Christian Hamel; Screening of PRPH2/RDS in patients with autosomal dominant retinitis pigmentosa reveals novel disease-causing mutations and 8.6% prevalence in French population. Invest. Ophthalmol. Vis. Sci. 2013;54(15):659.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

To determine the prevalence of mutations in peripherin-2/retinal degeneration slow (PRPH2/RDS) gene in a cohort of 245 French families with autosomal dominant retinitis pigmentosa (adRP).

 
Methods
 

Clinical investigations included visual field testing, fundus examination, OCT, autofluorescence testing and ERG recording. The 3 coding exons and adjacent intronic sequences of PRPH2/RDS were screened by Sanger sequencing. Genotyping was performed using microsatellite markers between D6S1575 and D6S1650 spanning approximately 3 Mb around PRPH2/RDS gene.

 
Results
 

Twelve - 5 novel and 7 previously described - mutations were found for 21 families (8.6%), including 3 missense (p.Asp194Glu, p.Trp246Cys and p.Leu254Gln), 1 frameshift (p.Val69CysfsX30) and 1 splice site (c.829-4C>G) novel mutations. They all co-segregated with the disease phenotype, and the novel mutations were not identified in ethnically matched controls. The severity of the disease was moderate with penetrance variations. Some patients showed vitelliform deposits or macular involvement. The novel p.Leu254Gln was found in 4 families originating from the same geographic origin. Affected patients shared the same haplotype suggesting a founder effect. One affected subject was homozygous. A novel spice-site mutation, c.829-4C>G, found in 3 families, was predicted to create a new acceptor splice site 3 bp upstream the natural splice site, leading to the in-frame insertion of a glutamine, p.Glu276_Val277insGln. The haplotypes of the 3 families were different.

 
Conclusions
 

The mutations in PRPH2/RDS account for 8.6% of adRP in the French population, making this gene a major cause of adRP in France after rhodopsin. This prevalence is higher than previously reported (1.3 to 2.9%), possibly because of underdiagnosed family members with mild disease, leading to erroneously classify them as simplex cases.

 
Keywords: 702 retinitis • 537 gene screening • 463 clinical (human) or epidemiologic studies: prevalence/incidence  
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