中华眼科杂志 2000年第1期第36卷 论著

作者：杨桦　罗成仁　周久模　严密　陈大年　黄倩

单位：杨桦（上海市第一人民医院眼科，200080）；罗成仁（成都，华西医科大学附属第一医院眼科　10041）；周久模（成都，华西医科大学附属第一医院眼科　10041）；严密（成都，华西医科大学附属第一医院眼科　10041）；陈大年（成都，华西医科大学附属第一医院眼科　10041）；黄倩（成都，华西医科大学附属第一医院眼科　10041）

关键词：视网膜色素变性；基因；表型；聚合酶链反应

　　【摘要】　目的　研究原发性视网膜色素变性（retinitis pigmentosa, RP）家系中缓慢型视网膜变性（retinal degeneration slow, 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（polymerase chain reaction, PCR）及限制性片段长度多态性（restriction fragment length polymorphism, 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216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216密码子的第2个核苷酸出现了C→T的突变（Pro216Leu）。RDS基因Pro216 Leu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Pro216 Leu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

YANG Hua, LUO Chengren, ZHOU Jiumo

　　（Department of Ophthalmology, First Clinical Medical School, West China University of Medical Sciences, Chengdu 610041，China）

　　【Abstract】　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.

　　【Key words】　Retinitis pigmentosa； Gene； Phenotype； Polymerase chain reaction

　　在遗传性视觉损害中，原发性视网膜色素变性（retinitis pigmentosa, RP）是致盲的最常见原因之一。在发展中国家，以往最常见的致盲性眼病如维生素A缺乏或感染所致的角膜瘢痕、白内障等的发病率现正在逐年降低，而包括RP在内的遗传性疾病则逐渐成为致盲的主要原因^［1］。研究表明缓慢型视网膜变性（retinal degeneration slow, RDS）基因又称盘膜边缘蛋白基因，其与RP发病相关，本研究对来自同一家系的中国人RP患者进行RDS基因突变的筛查，并对有基因突变的中国人RP患者的眼部表型进行分析，为从DNA水平研究RP的发病机制和进一步对RP进行合理分类提供理论基础。

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