title: [Mitochondrial genome analysis in the probands of six Chinese families with MELAS].
abstract: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a genetically heterogeneous disorder. The most prevalent mitochondrial DNA (mtDNA) mutation associated with MELAS is the m.3243A>G transition in the mitochondrial tRNA(Leu(UUR)) gene. Here, we report the clinical, genetic and molecular characterization of six probands from Han Chinese families with MELAS. Four of six probands carried the heteroplasmic m.3243A>G mutation. The levels of mutation load ranged from 29% to 59%, which were correlated with the severity of the clinical phenotypes. Two probands with MELAS/Leigh overlap were 3243 A>G negative, whose severity and relapse were greater than the other 4 probands. One proband with MELAS/Leigh harbored the known ND5 m.13094T>C mutation, which is related to MELAS/Leigh overlap and cerebella ataxia. Sequence analysis of entire mtDNA showed the distinct sets of variants including some variants that may be associated with diabetes, hearing loss, seizures, cardiomyopathy, and Leigh syndrome. Our data suggested that the phenotype and severity of MELAS mainly depend on the mutation load, and some variants may partially contribute to the phenotype and diversity. Our finding also highlighted the complexity of the relationship between genotype and phenotype in MELAS.
authors.affiliation: Institute of Genetics, College of Life Science, Zhejiang University, Hangzhou 310058, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology, Sir Run Run Shao Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
authors.forename: Shao
authors.initials: S
authors.lastname: Yuquan
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Baorong
authors.affiliation: Institute of Genetics, College of Life Science, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Pingping
authors.affiliation: 1. Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; 2. Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China;
authors.forename: Du
authors.initials: D
authors.lastname: Ailian
authors.affiliation: Institute of Genetics, College of Life Science, Zhejiang University, Hangzhou 310058, China.
authors.forename: Guan
authors.initials: G
authors.lastname: Minxin
mesh_terms: D000293:Adolescent; D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D054629:Genome, Mitochondrial; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial