慢性进行性眼外肌瘫痪和Kearns-Sayre综合征的线粒体DNA突变分析  

Mitochondrial DNA mutations in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome

作　　者：王朝霞[1] 袁云[1] 高枫[1] 戚豫[2] 沈定国[3] 陈清棠[1] 

机构地区：[1]北京大学第一医院神经内科,100034 [2]北京大学第一医院中心实验室,100034 [3]301医院神经科

出　　处：《中华医学遗传学杂志》2003年第4期273-278,共6页Chinese Journal of Medical Genetics

基　　金：北京大学人类疾病基因中心资助项目 (2 0 0 0 - A1 4 )~~

摘　　要：目的　探讨慢性进行性眼外肌瘫痪 (chronic progressive external ophthalmoplegia,CPEO)和 Kearns- Sayre综合征 (Kearns- Sayre syndrome,KSS)的线粒体 DNA (mitochondrial DNA,mt DNA)突变特点。方法　用 Southern印迹方法检测 7例 CPEO和 4例 KSS患者的肌肉组织 mt DNA,并进一步用聚合酶链反应产物直接测序来明确缺失的具体范围 ;用聚合酶链反应 -限制性内切酶分析法检测有无 mt D-NA A32 4 3G点突变。结果　发现 5例患者 (2例 CPEO和 3例 KSS)存在 mt DNA的大片段缺失 ;1例 KSS患者存在 A32 4 3G点突变。 5例大片段缺失的大小及缺失范围各不相同 ,从 3.0～ 8.0 kb不等 ,缺失型 mt D-NA占总 mt DNA的比例为 37.6 %～ 87.0 %。聚合酶链反应产物测序表明这 5例缺失类型均未见文献报道。结论　与 CPEO和 KSS患者相关的最常见的 mt DNA突变为大片段缺失 ,A32 4 3G点突变也可在少数患者中检测到。Objective: Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) belong to neurological diseases caused by a defect in the energy-producing system of mitochondria, and are known to be associated with a deletion in the mitochondrial genome. This study was aimed to understand with greater clearness the characteristics of mitochondrial DNA (mt DNA) mutations in 11 Chinese patients with CPEO (7 cases) or KSS (4 cases). Methods: Densitometry of the bands on Southern blot, polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing were performed to search large scale deletions and A3243G point mutation in patients' muscle mtDNA. Results: Large deletions in mtDNA were detected in 2 CPEO and 3 KSS patients, the size of deletion ranged from 3. 0 kb to 8. 0 kb. Moreover, mtDNA A3243G point mutation was identified in 1 KSS patient. The proportion of mutant mtDNA was 37. 6%-87. 0%. Direct sequencing of the PCR products revealed 5 novel large deletions not reported by others. Conclusion: The findings in this study being consistent with the reports by others, large scale deletions of mtDNA are frequently found in Chinese patients with KSS and CPEO. mtDNA A3243G mutation may also exist in some patients with KSS and CPEO.

关 键 词：慢性进行性眼外肌瘫痪 KEARNS-SAYRE综合征 线粒体DNA 基因突变 聚合酶链反应 线粒体脑肌病 

分 类 号：R746[医药卫生—神经病学与精神病学]