线粒体DNA单一大片段缺失患者61例临床表型和基因型分析  

Clinical phenotype and genotype analysis in 61 patients with large scale single deletion in mitochondrial DNA

作　　者：刘祺[1] 刘靖[1] 冷颖琳 赵娟[1] 吕鹤[1] 张巍[1] 袁云[1] 王朝霞[1] 

机构地区：[1]北京大学第一医院神经内科,100034

出　　处：《中华神经科杂志》2015年第5期382-389,共8页Chinese Journal of Neurology

基　　金：科技部“十二五”重大专项课题（2011ZX09307-001-07）;国家自然科学基金资助项目（30870864,81341040）

摘　　要：目的 报道携带线粒体DNA（mitochondrial DNA,mtDNA）缺失患者的临床表型和基因型特点,分析二者之间的相关性.方法 对经临床和肌肉病理检查诊断为线粒体病的70例患者,提取其肌肉组织DNA,进行长程PCR-多酶联合酶切-短循环PCR产物直接测序法检测mtDNA有无大片段缺失,并明确缺失的具体位置.总结携带mtDNA缺失的患者的临床表型,分析mtDNA缺失长度与临床表型之间的相关性.结果 在61例患者的肌肉mtDNA发现单一大片段缺失,其中慢性进行性眼外肌麻痹（CPEO） 54例、Kearns-Sayre综合征（KSS）6例和线粒体脑肌病伴卒中样发作和高乳酸血症1例,所有患者均无家族史.患者的发病年龄1～55岁.61例患者中共检测到37种缺失类型,其中4 977 bp的“普通缺失”占39.3％（24/61）.CPEO患者mtDNA缺失的平均长度为（5 052.17±1 390.96） bp,KSS患者缺失为（5 703.33±1 242.73） bp,两组患者间差异无统计学意义.线粒体DNA缺失长度和患者起病年龄呈负相关（r=-0.415,P=0.001）.结论 线粒体DNA单一大片段缺失主要导致CPEO和KSS,缺失片段长者发病早.mtDNA“普通缺失”在我国患者中也常见.Objective To investigate the clinical and genetic characteristics of a cohort of Chinese patients with large-scale single deletion in mitochondrial DNA （mtDNA）.Methods Long-range PCR was performed to search large scale deletions in 70 patients＇; muscle mtDNA who were diagnosed with mitochondrial disease by clinical and muscle pathological examination.Then multiple restriction enzyme digestion of long-range PCR product followed by short-cycle PCR were used to define the exact size and location of large-scale deletions.We summarized the clinical phenotypes of patients,and analyzed the correlations between clinical phenotypes and size of mtDNA deletions in those patients with single large-scale deletion.Results Sixty-one patients were identified to have single large-scale deletion in their muscle mtDNA,including 54 patients with chronic progressive external ophthalmoplegia （CPEO）,6 with KearnsSayre syndrome （KSS） and 1 with mitochondrial myopathy,encephalopathy,lactic acidosis and stroke-like episodes.Totally 37 patterns of mtDNA deletions were detected in this cohort of patients.The “common deletion”,4 977 bp deletion appeared in 39.3% （24/61） patients.The mean size of single deletion in CPEO patients was （5 052.17 ± 1 390.96） bp,while in KSS patients it was （5 912.43 ± 1 262.15） bp.There was no significant difference between CPEO patients group and KSS patients group.The size of deletions was correlated with onset age （r =-0.415,P =0.001）.Conclusions Large-scale single deletion of mtDNA mainly causes CPEO and KSS.Patients with larger deletions present with earlier onset of disease.The mtDNA “common deletion” is also common in Chinese patients.

关 键 词：眼肌麻痹 慢性进行性外侧 卡恩斯-塞尔综合征 DNA 线粒体 表型 基因型 聚合酶链反应 

分 类 号：R596[医药卫生—内科学]