线粒体脑肌病伴高乳酸血症和卒中样发作综合征的线粒体DNA突变特点

Analysis of mitochondrial DNA A3 243G point mutation in 9 cases with mitochondrial encephalomyopathy,lactic acidosis and stroke-like episodes

目的 探讨线粒体脑肌病伴高乳酸血症和卒中样发作 (MELAS综合征 )的分子遗传学特点。方法 用聚合酶链反应 限制片段长度多态性 (PCR RFLP)方法检测来自 7个家庭的 9例MELAS患者及其部分母系亲属的肌肉和 (或 )外周血细胞的mtDNA的A3 2 4 3G和T3 2 71C点突变 ,并进行突变型mtDNA的定量。结果 在 9例患者和 1例亲属的肌肉和 (或 )外周血细胞中检测到A3 2 4 3G点突变 ,未检测到T3 2 71C突变。在这 10例A3 2 4 3G阳性标本中 ,外周血细胞 ( 9例 )的突变型mtDNA的比例为 2 6 8%～ 5 0 3 % ;肌肉组织 ( 4例 )的突变型mtDNA的比例为 4 6 8%～ 61 0 % ;对 3例患者同时进行了肌肉和血细胞标本的检测 ,突变型mtDNA的比例肌肉组织均高于血细胞。对 6个家庭的部分母系亲属的血细胞研究表明 :只有 1例先证者的同胞有此突变 ;另外 3例先证者的母亲及 2例先证者的同胞均未检测到此突变。另外有 2例先证者的儿子临床表现符合MELAS ,血中也检测到此突变。结论 mtDNAA3 2 4 3G突变在本组MELAS综合征中的发生率较高 ,并且可在不同组织中检测到此突变 ,与国外文献报道一致 ;但国外报道多为母系遗传 ,而我们的病例以散发的居多 ,推测是由于新生突变所致。

Objective To study the characteristics of molecular genetics concerning Chinese mitochondr ial encephalomyopathy,lactic acidosis and stroke-like episodes (MELAS). Methods A3243G and T3271C point mutations in the mtDNA of muscle and (or) blood cells were investigated in 9 patients with MELAS and some o f their maternal relatives from 7 families by using PCR-RFLP. Furthermore,mut ant mtDNA in the sample harboring mutation was quantitatively analysed. Results The mtDN A A3243G point mutation was unanimously identified in tissues of all patients an d 1 of their relatives. However,the T3271C point mutation was identi f ied in none of series in our study. The proportion of mtDNA A3243G was 46.8%～ 61. 0% in muscle (4 cases) as well as 26.8%～50.3% in blood (9 cases). In the 3 p atie nts with muscles and blood cells available,their mutant mtDNA proportion in mus cle is consistently higher than in blood cells. The study of leukocytes of some maternal relatives from 6 families showed that,while only 1 proband had a siste r harboring A3243G mutation and none of the mothers of another 3 probands or sib lings of the other 2 probands had the point mutation. However,the sons of 2 pr o bands had not only phenotype of MELAS,but also mtDNA A3243G point mutation in t heir blood. Conclusion mtDNA A3243G mutation highly exists in the series with M E LAS syndrome in our study and can be detected in various tissues,which is consi stent with reports abroad. However,most of our cases are sporadic rather than m aternal inherited. It is presumedly caused by a de novo mutation. Whether i t is due to ethnic difference or sporadic event needs to be investigated further.