title: A MELAS syndrome family harboring two mutations in mitochondrial genome.
abstract: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous mitochondrial disorder with variable clinical symptoms. Here, from the sequencing of the entire mitochondrial genome, we report a Korean MELAS family harboring two homoplasmic missense mutations, which were reported 9957T>C (Phe251Leu) transition mutation in the cytochrome c oxidase subunit 3 (COX3) gene and a novel 13849A>C (Asn505His) transversion mutation in the NADH dehydrogenase subunit 5 (ND5) gene. Neither of these mutations was found in 205 normal controls. Both mutations were identified from the proband and his mother, but not his father. The patients showed cataract symptom in addition to MELAS phenotype. We believe that the 9957T>C mutation is pathogenic, however, the 13849A>C mutation is of unclear significance. It is likely that the 13849A>C mutation might function as the secondary mutation which increase the expressivity of overlapping phenotypes of MELAS and cataract. This study also demonstrates the importance of full sequencing of mtDNA for the molecular genetic understanding of mitochondrial disorders.
authors.affiliation: Department of Neurology and Ewha Medical Research Center, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Hwang
authors.forename: Joonki
authors.initials: J
authors.lastname: Kim
authors.forename: Eun Min
authors.initials: EM
authors.lastname: Cho
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Cho
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Hyang Woon
authors.initials: HW
authors.lastname: Lee
authors.forename: Song Ja
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
mesh_terms: D000328:Adult; D044466:Asian People; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics*; D005260:Female; D006801:Humans; D007723:Korea; D017241:MELAS Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C481838:MT-ND5 protein, human; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I