title: Novel mutations m.3959G>A and m.3995A>G in mitochondrial gene MT-ND1 associated with MELAS.
abstract: Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are progressive neurodegenerative disorder associated with polygenetic, maternally inherited mutations in mitochondrial DNA. Approximately 80% of MELAS cases are caused by the mutation m.3243A>G of the mitochondrial tRNA(Leu (UUR)) gene (MT-TL1). We reported two probands with MELAS features. Muscle biopsy identified ragged-red fibers (RRF) in Gomori Trichrome staining. A respiratory chain function study showed decreased activity of mitochondrial respiratory chain complex I in both probands. Sequencing of the mitochondrial DNA revealed two novel MT-ND1 gene missense mutations, m.3959G>A and m.3995A>G, which are highly conserved among species. Protein secondary structure predictions demonstrated that these mutations may alter the peptide structure and may lead to decreased ND1 gene stability. Our findings suggest that these two novel mutations may contribute to the MELAS phenotypes of the patients in our study.
authors.affiliation: Department of Neurology, Huashan Hospital .
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Chong-Bo
authors.initials: CB
authors.lastname: Zhao
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Lu
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Wang
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Zhu
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Xi
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Su-Shan
authors.initials: SS
authors.lastname: Luo
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Xiao
authors.forename: Chuan-Zhen
authors.initials: CZ
authors.lastname: Lu
mesh_terms: D000328:Adult; D001483:Base Sequence; D001706:Biopsy; D001921:Brain / Q000473:pathology; D002681:China; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D004569:Electroencephalography; D042967:Electron Transport Complex I / Q000378:metabolism*; D054629:Genome, Mitochondrial / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D009245:NADH Dehydrogenase / Q000235:genetics*; D010375:Pedigree; D011487:Protein Conformation; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D042967:Electron Transport Complex I; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human