ABSTRACT
Introduction: Retinitis pigmentosa (RP) is a group of hereditary retinal diseases in which photoreceptor cells degenerate. It is both clinically and genetically heterogenous. Using a twostage approach by combining linkage analysis with mutation detection, we have rapidly identified the gene locus and the mutation site of a Chinese Singaporean family with autosomal dominant RP. Materials and Methods: Three Chinese Singaporean families were tested. One family showed autosomal dominant inheritance pattern, while the other two could be recessive or sporadic. Twelve di-nucleotide markers tightly linked to 6 genes known to be responsible for either autosomal dominant or recessive RP were selected for linkage analysis. Cosegregation of marker and disease inheritance pattern permits identification of the target candidate gene. RFLP (restriction fragment length polymorphism) markers were added to confirm the linkage result prior to the detailed mutation detection study. Results: With this two-stage strategy, the autosomal dominant RP family showed the rhodopsin locus segregating concordantly with the disease. Mutation screening later identified a nonsense mutation 5261C>T in the last exon of rhodopsin gene. It predicted a Q344X changes at the C-terminus of the gene product, truncating it by 5 amino acids. Conclusion: This systematic approach facilitates molecular diagnosis of a genetically heterogenous disease like RP. This is the first report of an RP mutation in Singapore. This 5261C>T mutation has been reported in the Caucasian, but not the Chinese population. The relatively milder phenotype in this family showed similarity to the reported US family, indicating the correlation of mutation site to severity of disease regardless of ethnicity.
Retinitis pigmentosa (RP, MIM#26800) is a group of hereditary retinal diseases that feature progressive photoreceptor degeneration, eventually leading to partial or complete blindness. It is characterised by night blindness and constricted visual field caused by the early loss of peripheral photoreceptors, primarily rods. Central vision could also be lost as the disease progresses. It classically shows fundus changes such as intraretinal pigmentation, narrowed arterioles and optic disc pallor. RP is a common form of inherited blindness worldwide. Epidemiological studies around the world consistently report a frequency of approximately 1 in 4000 to 5000 without apparent ethnic and racial distinctions.1,2
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