原发性视网膜色素变性家系的RDS基因Pro216Leu突变及其表型研究

目的　研究原发性视网膜色素变性 (retinitispigmentosa ,RP)家系中缓慢型视网膜变性(retinaldegenerationslow ,RDS)患者的RDS基因突变与临床表型的关联 ,以探讨RP的发病机制。方法对来自同一家系的 2例RP患者及 2例正常人外周血DNA进行分子遗传学分析 ,采用聚合酶链反应(polymerasechainreaction ,PCR)及限制性片段长度多态性 (restrictionfragmentlengthpolymorphism ,RFLP)技术 ,筛查RDS基因突变 ,对有突变的RDS基因片段进行克隆测序及分析 ,同时进行家系分析及眼部临床检查。结果　来自同一家系的 2例RP患者均查出有RDS基因 2 16密码突变 ,而 2例正常人未查出上述突变。经测序证实RDS基因 2 16密码子的第 2个核苷酸出现了C→T的突变 (Pro2 16Leu)。RDS基因Pro2 16Leu突变的眼部临床表型为视力损害严重的弥漫型RP ,伴有黄斑部病变。结论　中国人RP患者存在RDS基因Pro2 16Leu突变 ;其眼部表型为弥漫型RP伴有黄斑部病变。

The study of RDS gene mutation and clinical phenotype in a family with primary retinitis pigmentosa

Objective To investigate retinal degeneration slow (RDS) gene mutation in a Chinese family with primary retinitis pigmentosa (RP) and the association of the mutation with clinical phenotypes and to explore the pathogenesis of RP Methods Blood DNA from 2 patients in the same family with RP and 2 normal persons was analyzed by molecular genetic methods RDS gene mutation was screened out by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis The mutant RDS gene fragment was cloned, then sequenced with an automatic DNA sequencer using a dideoxy chain termination protocol The phenotype of the patients with the gene mutation were examined and determined by clinical ophthalmologic examinations Results The PCR RFLP analysis of the RDS gene in 2 patients with RP revealed codon 216 mutation of RDS gene The mutation was heterozygous, and not found in 2 normal persons as controls The alteration in the DNA sequence was identified as a heterozygous transversional change of C to T at the second nucleotide in codon 216 of RDS gene, resulting in the amino acid replacement of proline residue with leucine residue (Pro216Leu) The ocular finding of the patients with Pro216Leu mutation of RDS gene included severe visual loss and diffuse distribution of pigmentary changes with macular degeneration Conclusions The Pro216Leu mutation of RDS gene is found in Chinese patients with RP The gene mutation is associated with the ocular phenotype, diffuse RP with macular degeneration