Spectrum of Rhodopsin Mutations in French Autosomal Dominant Rod–Cone Dystrophy Patients
Open Access
- 1 July 2010
- journal article
- research article
- Published by Association for Research in Vision and Ophthalmology (ARVO) in Investigative Opthalmology & Visual Science
- Vol. 51 (7), 3687-3700
- https://doi.org/10.1167/iovs.09-4766
Abstract
Purpose.: To identify the prevalence of rhodopsin (RHO) mutations in French patients with autosomal dominant rod–cone dystrophies (adRPs). Methods.: Detailed phenotypic characterization was performed, including precise family history, best corrected visual acuity with the ETDRS chart, slit lamp examination, kinetic and static perimetry, full-field and multifocal electroretinography (ERG), fundus autofluorescence imaging (FAF), and optical coherence tomography (OCT). For genetic diagnosis, genomic DNA of 79 families was isolated by standard methods. The coding exons and flanking intronic regions of RHO were PCR amplified, purified, and sequenced in the index patient. Results.: Of this French adRP sample, 16.5% carried an RHO mutation. Three different families showed a novel mutation (p. Leu88Pro, p.Met207Lys and p.Gln344Pro), while ten unrelated families showed recurrent, previously published mutations (p.Asn15Ser, p.Leu131Pro, p.Arg135Trp, p.Ser334GlyfsX21 and p.Pro347Leu). All mutations co-segregated with the phenotype within a family, and the novel mutations were not identified in control samples. Conclusions.: This study revealed that the prevalence of RHO mutations in French adRP patients is in accordance with that in other studies from Europe. Most of the changes identified herein reflect recurrent mutations, within which p.Pro347Leu substitution is the most prevalent. Nevertheless, almost one fourth of the changes are novel, indicating that, although RHO is the first gene implicated and probably the most studied gene in RP, it is still important performing mutation analysis in RHO to detect novel changes. The detailed phenotype–genotype analyses in all available family members deliver the basis for therapeutic approaches in those families.Keywords
This publication has 44 references indexed in Scilit:
- ISCEV Standard for full-field clinical electroretinography (2008 update)Documenta Ophthalmologica, 2008
- ISCEV guidelines for clinical multifocal electroretinography (2007 edition)Documenta Ophthalmologica, 2007
- Prevalence of Disease-Causing Mutations in Families with Autosomal Dominant Retinitis Pigmentosa: A Screen of Known Genes in 200 FamiliesPublished by Association for Research in Vision and Ophthalmology (ARVO) ,2006
- Different Amino Acid Substitutions at the Same Position in Rhodopsin Lead to Distinct PhenotypesPublished by Association for Research in Vision and Ophthalmology (ARVO) ,2006
- Molecular genetics of autosomal dominant retinitis pigmentosa (ADRP): a comprehensive study of 43 Italian familiesJournal of Medical Genetics, 2005
- Genotype-phenotype correlation in a family with Arg135Leu rhodopsin retinitis pigmentosaBritish Journal of Ophthalmology, 2004
- A linkage survey of 20 dominant retinitis pigmentosa families: frequencies of the nine known loci and evidence for further heterogeneity.Journal of Medical Genetics, 1998
- Three novel rhodopsin mutations (C110F, L131P, A164V) in patients with autosomal dominant retinitis pigmentosaHuman Molecular Genetics, 1994
- Molecular Analysis and Genetic Mapping of the Rhodopsin Gene in Families with Autosomal Dominant Retinitis PigmentosaGenomics, 1993
- Autosomal dominant ‘sector’ retinitis pigmentosa due to a point mutation predicting an Asn-15-Ser substitution of rhodopsinHuman Molecular Genetics, 1993