title: Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia.
abstract: Leber hereditary optic neuropathy and dystonia (LDYT) is a mitochondrial disorder associated with variable combinations of vision loss and progressive generalized dystonia. LDYT is a unique oxidative phosphorylation disorder caused by mutations in mitochondrial ND6 or ND4 gene. In this paper, we describe a Chinese family with 18 LDYT patients. The comprehensive nucleotide sequence analysis of the entire mitochondrial genome using resequencing microarray revealed a mutation (mtND3*10197A (m.10197G>A)) substituting a threonine for a highly conserved alanine at codon 47 of MTND3 on the background of haplogroup D4b. Quantitative analysis of the heteroplasmy of the mutation revealed a homoplasmy in the leukocytes of all the affected individuals on the maternal side. This is the first description of the ND3 mutation causing LDYT. The mtND3*10197A (m.10197G>A) mutation has recently been described in French and Korean patients with Leigh syndrome. These findings suggest that the clinical presentations associated with the mtND3*10197A (m.10197G>A) mutation (ND3) are much wider, encompassing those of LDYT and Leigh syndrome.
authors.affiliation: Department of Pathology and Pathophysiology, Graduate School, Peking Union Medical College, Beijing, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Wang
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Zong-Liang
authors.initials: ZL
authors.lastname: Gao
authors.forename: Guo-Xiang
authors.initials: GX
authors.lastname: Wang
authors.forename: Xian-Wen
authors.initials: XW
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Goto
authors.forename: Jin-Ning
authors.initials: JN
authors.lastname: Lou
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004421:Dystonia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D042967:Electron Transport Complex I / Q000235:genetics*; D005123:Eye / Q000473:pathology; D005260:Female; D050259:Genes, Mitochondrial; D006801:Humans; D007888:Leigh Disease / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D042967:Electron Transport Complex I; C114961:MT-ND3 protein, human