Phenotypic intrafamilial variability associated with S212G mutation in the RDS/peripherin gene

PURPOSE: To describe an Italian family in which two separate phenotypes (retinitis pigmentosa and adult onset vitelliform macular dystrophy) are associated with an identical mutation (S212G) in the peripherin/RDS gene. This mutation has already been reported in patients with retinitis pigmentosa, but it has never been previously detected in association with adult onset vitelliform macular dystrophy. METHODS: A 38-year-old woman complained of bilateral mild metamorphopsias and on ophthalmologic examination she showed the clinical phenotype of adult onset vitelliform macular dystrophy. Her 62-year-old mother was clinically diagnosed with a retinitis pigmentosa, with a severe clinical course. RESULTS: In both patients, molecular genetic analysis revealed a 874A-->G transition in the exon 2 of the RDS gene leading to the amino acid change of S212G. CONCLUSIONS: Peripherin/RDS S212G mutation may have damaging effects on the formation and stability of the photoreceptors' disk structure and may be associated with different clinical phenotypes, even in the same family. Intrafamilial phenotypic variability has been reported for other RDS mutations; this supports the possible influence of modifier genes or environmental factors in the clinical expression of RDS gene variants. Moreover, it suggests that in patients with retinal degeneration and peripherin/RDS mutation, caution should be taken both in using molecular genetic results to predict the clinical course of the disease and in offering genetic counseling. PMID: 18050133 [PubMed - indexed for MEDLINE]