title: Mutations in mitochondrially encoded complex I enzyme as the second common cause in a cohort of Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.
abstract: The mutation pattern of mitochondrial DNA (mtDNA) in mainland Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) has been rarely reported, though previous data suggested that the mutation pattern of MELAS could be different among geographically localized populations. We presented the results of comprehensive mtDNA mutation analysis in 92 unrelated Chinese patients with MELAS (85 with classic MELAS and 7 with MELAS/Leigh syndrome (LS) overlap syndrome). The mtDNA A3243G mutation was the most common causal genotype in this patient group (79/92 and 85.9%). The second common gene mutation was G13513A (7/92 and 7.6%). Additionally, we identified T10191C (p.S45P) in ND3, A11470C (p. K237N) in ND4, T13046C (p.M237T) in ND5 and a large-scale deletion (13025-13033:14417-14425) involving partial ND5 and ND6 subunits of complex I in one patient each. Among them, A11470C, T13046C and the single deletion were novel mutations. In summary, patients with mutations affecting mitochondrially encoded complex I (MTND) reached 12.0% (11/92) in this group. It is noteworthy that all seven patients with MELAS/LS overlap syndrome were associated with MTND mutations. Our data emphasize the important role of MTND mutations in the pathogenicity of MELAS, especially MELAS/LS overlap syndrome.
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Danhua
authors.initials: D
authors.lastname: Zhao
authors.forename: Daojun
authors.initials: D
authors.lastname: Hong
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Qi
authors.forename: He
authors.initials: H
authors.lastname: Lv
authors.forename: Riliang
authors.initials: R
authors.lastname: Zheng
authors.forename: Liqun
authors.initials: L
authors.lastname: Feng
authors.forename: Yining
authors.initials: Y
authors.lastname: Huang
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000737:chemistry*; D042967:Electron Transport Complex I / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D017241:MELAS Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000473:pathology; D009154:Mutation; D009245:NADH Dehydrogenase / Q000737:chemistry / Q000235:genetics; D010641:Phenotype; D011487:Protein Conformation; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; C098483:NADH dehydrogenase subunit 4; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I