Two Novel Missense Mutations in the Peripherin/RDS Gene in two Unrelated French Patients with Autosomal Dominant Retinitis Pigmentosa

Abstract

Purpose

To report the identification of two novel RDS mutations in the peripherin/RDS gene of two unrelated French patients affected by autosomal dominant retinitis pigmentosa (ADRP).

Methods

Fifty-eight unrelated patients affected by ADRP were analyzed. Our diagnostic criteria for RP were bilateral fundus involvement, concentric depression of the visual field and severe involvement on electroretinogram. Transmission of the trait was unambiguous. Our strategy was to analyze the coding sequence of the gene using a combination of single-strand conformation polymorphism (SSCP) and direct sequence analysis of the exons of the gene. Exons that displayed conformational polymorphisms were sequenced on an automated DNA sequencer.

Results

The sequence analyses revealed two previously unreported missense mutations: Cys165Tyr and Phe211Leu in exons 1 and 2, respectively. None of the 70 controls analyzed carried these base changes. Cosegregation of the base substitution with the disease could be tested in both families presenting the Cys165Tyr and Phe211Leu mutations.

Conclusions

Several lines of evidence support the idea that these base substitutions are disease-causing mutations. To the best of our knowledge, no peripherin/RDS gene analysis has been previously reported in ADRP in France.

Keywords

Peripherin RDS Gene Mutations Retinitis pigmentosa

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