常染色体隐性遗传视网膜色素变性家系视紫红质基因突变的检测分析

Analysis of the mutation of rhodopsin gene in an inbreeding family with autosomal recessive retinitis pigmentosa

目的 观察一个近亲婚配常染色体隐性遗传视网膜色素变性 (ARRP)家系中视紫红质基因(RHO)的突变特征 ,并探讨其视网膜色素变性 (RP)发病机制。 方法 抽取 8例该 ARRP家系成员及 10例正常对照者的外周静脉血 5～ 8ml;提取基因组 DNA;采用聚合酶链反应 (PCR)方法扩增 RHO基因第1～ 5外显子和第 1内含子基因片段 ,用直接 DNA测序法筛查 RHO基因突变。 结果 来自同一家系 3例患者 RHO基因的第 5外显子第 344密码子发生了 A→ G碱基的错义突变 ,导致了谷氨酰胺变成了精氨酸(Gln344 Arg) ,3例患者为该突变的纯合子。患者近亲婚配父母及 1例未患病家庭成员为该突变的杂合子。2例未患病家庭成员及 10例正常对照者均未发现 RHO基因突变。 结论 Gln344 Arg突变可能是该ARRP家系的致病原因 ;在近亲婚配 ARRP家系中 RHO基因突变频率可能增加。

Objective To detect characteristics and the pathogenesis of rhodopsin (RHO) gene mutation in an inbreeding family with autosomal recessive retinitis pigmentosa (ARRP). Methods Peripheral venous blood 5-8 ml was abstracted from 8 members in the inbreeding ARRP family and 10 control individuals. DNA gene group was picked. Extron 1-5 of RHO gene was amplified by polymerase chain reaction (PCR),and the mutation of RHO gene was screened by direct DNA sequence measurement. Results The Gln-344-Arg mutation in the RHO gene was detected in 3 patients with ARRP and homozygotes of the mutation in 3 patients were found. Heterozygous of the mutation was detected in the parent of patients and 1 healthy family member. No mutation of RHO gene was found in 2 healthy family members and 10 control individuals. Conclusions The Gln-344-Arg mutation in the RHO gene may be the pathogenic factor of the ARRP family; the frequency of the mutation of RHO gene may increase in the inbreeding ARRP family.