Intrafamilial phenotypic variability in families with RDS mutations: exclusion of ROM1 as a genetic modifier for those with retinitis pigmentosa

Abstract

Objectives: To identify suspected RDS mutations in families in which different people have been identified with either generalised retinal dystrophy or macular dystrophy.

Methods: Two families with a retinal dystrophy were extensively phenotyped and blood was taken for mutation analysis of the RDS (all) and ROM1 (retinitis pigmentosa patients only) genes.

Results: A novel p.Trp94X mutation in RDS was found in all three affected members of a two-generation family that was associated with retinitis pigmentosa in the son, pattern dystrophy in the daughter and fundus flavimaculatus in the mother. In the second family, the proband with retinitis pigmentosa carried a p.Arg220Trp mutation. The mother, who was unavailable for mutation screening, had adult vitelliform macular dystrophy. No ROM1 mutations were found in those with retinitis pigmentosa in either family.

Conclusion: Mutations in RDS can be associated with an intrafamilial variation in retinal disease. The phenotypes range from Stargardt-like macular dystrophy to classic retinitis pigmentosa.

Clinical relevance: Intrafamilial phenotypic variation may be due to the presence of environmental or genetic modifying factors. The presence of a modifying-sequence change in the coding region of ROM1 for two people with retinitis pigmentosa from two families with intrafamilial variation in RDS mutation phenotype has been excluded in this study.