Li Weiwei, Zhang Wei, Li Fang, Wang Cailing
Department of Endocrinology, Qianfoshan Hospital, Shandong University 66 Jingshi Road, Jinan 250014, China.
Int J Clin Exp Pathol. 2015 Jun 1;8(6):7022-7. eCollection 2015.
To investigate the mitochondrial mutations in patients suffering from both mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) and maternally inherited diabetes. MELAS was confirmed by muscle biopsy performed from the biceps muscle of the proband. Mitochondrial DNA (mtDNA) was isolated from peripheral blood mononuclear cells. The significant mtDNA loci of other 14 family members were further detected according to the sequencing results of the proband. Direct sequencing of PCR products was used to identify the mitochondrial mutations. The proband (III 1) and her brother (III 3) both harbored the tRNALeu (UUR) A3243G mutation, with heteroplasmic levels of 50% and 33% respectively. Moreover, another two mitochondrial variants, A8860G and A15326G, were also detected in the samples of all the family members. MELAS and diabetes can coexist in one patient, and the main cause for these diseases is the tRNALeu (UUR) A3243G mutation. However, other gene variants may contribute to its pathogenesis. This case also supports the concept that both syndromes can be regarded as two phenotypes of the same disease.
为了研究患有线粒体脑肌病伴乳酸酸中毒和卒中样发作(MELAS)以及母系遗传糖尿病患者的线粒体突变情况。通过对先证者肱二头肌进行肌肉活检确诊为MELAS。从外周血单个核细胞中分离出线粒体DNA(mtDNA)。根据先证者的测序结果,进一步检测其他14名家庭成员的重要mtDNA位点。采用PCR产物直接测序法鉴定线粒体突变。先证者(III 1)及其兄弟(III 3)均携带tRNALeu(UUR)A3243G突变,异质性水平分别为50%和33%。此外,在所有家庭成员的样本中还检测到另外两个线粒体变异体A8860G和A15326G。MELAS和糖尿病可在同一患者中共存,这些疾病的主要病因是tRNALeu(UUR)A3243G突变。然而,其他基因变异可能也参与了其发病机制。该病例也支持这两种综合征可被视为同一种疾病的两种表型这一概念。