Prevalence of Rhodopsin mutations in autosomal dominant Retinitis Pigmentosa in Spain: clinical and analytical review in 200 families

Abstract

Purpose: We aimed to determine the prevalence of mutations in the RHO gene in Spanish families with autosomal dominant Retinitis Pigmentosa (adRP), to assess genotype-phenotype correlations and to establish an accurate diagnostic algorithm after 23 years of data collection.

Patients and methods: Two hundred patients were analysed through a combination of denaturing gradient gel electrophoresis, single-strand conformation polymorphism, genotyping microarray and Sanger sequencing of the RHO gene.

Results: Overall, 42 of 200 Spanish adRP families were mutated for RHO (21.0%). Twenty-seven different RHO mutations were detected; seven of them were novel. A genotype-phenotype correlation was established with clinical data from 107 patients. The most prevalent p.Pro347Leu mutation, responsible for 4.5% (9/200) of all mutated adRP families, was associated with a phenotype of early onset and severe course diffuse RP.

Conclusions: This retrospective study provides a wide spectrum of mutations in the RHO gene in Spanish patients with adRP. Also, the prevalence of mutations is similar to that reported in European population. Genotyping microarray followed by RHO sequencing is proposed as a first step in molecular diagnosis of adRP Spanish families. An increasing understanding of causal RHO alleles in adRP facilitates disease diagnosis and prognosis, especially for the prevalent p.Pro347Leu mutation.

Keywords: RHO; Retinitis Pigmentosa; Spanish families; autosomal dominant; diagnostic algorithm; genotype-phenotype correlation.