Objective: To evaluate the incidence and pattern of rhodopsin (RHO) mutations in Chinese patients with retinitis pigmentosa (RP). Methods: Conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing were applied to detect point mutations that occurred in the five coding exous and splice sites of RHO gene in 98 index patients with RP. Results: Four patients of one ADRP family were found to have a missense mutation at codon 347, Pro347Leu. One late-onset RP patient and her daughter, without clinical expression at present, were discovered to have a novel frameshift mutation at codon 327, Pro327 ( 1-bp del). Neither of the two mutations was found in 100 normal controls. Ala299Ser was found in one RP patient. Two control subjects also had Ala299Ser, suggesting its nonpathogenicity and just single nucleotide polymorphism (SNP). Conclusion: Two RP patients had rhodopsin mutations, thus the expected frequency of RHO mutations in RP is about 2.0% (95% confidence interval: 0.3% - 4.4% ). A highly conserved C-terminal sequence QVS (A)PA was altered due to Pro347Leu and thereby misdirecting rhodopsin to incorrect subcellular location. Loss of all phosphorylation sites at the C-terminus and a highly conserved sequence QVS(A)PA may occur because of Pro327( 1-bp del). To elucidate the predominant biochemical defects in such mutant, transgenic mice and transfected culture cells carrying Pro327( 1-bp del) would be of great value.
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