Objective: Autosomal dominant (AD) inheritance accounts for 15-20% of retinitis pigmentosa (RP) familial cases. The characterization of AD RP-related mutations remains essential because it provides both accurate diagnosis and clinically important prognostic information. Rhodopsin (RHO) and peripherin/RDS are the two most common mutated genes in AD RP in several series. However, the genetic characterization of patients from distinct ethnic groups will help to define the relative contribution of particular AD RP-related genes. In the present study, a search for causal mutations in RHO and peripherin/RDS in a group of 28 Mexican RP probands with AD inheritance was performed.
Methods: Methods included complete ophthalmologic examination as well as fluorangiographic and electroretinographic assessment. Molecular analysis included Polymerase (PCR) amplification and direct nucleotide sequencing of the coding exons of RHO and peripherin/RDS in DNA from affected subjects. Mutation-carrying exons were analyzed in a total of 29 first-degree relatives from some of these families.
Results: Five RHO mutations, including two novel ones and three previously reported, were demonstrated in this RP sample. Novel mutations were c.365A>G in exon 2 (Glu122Gly), and c.233A> in exon 1 (Asn78Ile). The other three RHO mutations were Phe45Leu, Arg135Trp, and Ser186Trp. No peripherin/RDS gene mutations were demonstrated in the remaining 23 probands.
Conclusion: Our study adds to the mutational spectrum of adRP by identifying two novel RHO mutations. RHO mutations were responsible of 17% of AD RP Mexican cases, a figure slightly lower to that found in other ethnic groups. Peripherin/RDS mutations are apparently an uncommon cause of AD RP in this population.