title: Alternative, simultaneous complex I mitochondrial DNA mutations in Leber's hereditary optic neuropathy.
abstract: Leber's hereditary optic neuropathy has been linked to a mitochondrial DNA mutation at position 11,778 in the ND-4 gene in 50% of families. Three alternative mutations in Complex I genes at positions 4,216 (ND-1), 4,917 (ND-2), and 13,708 (ND-5) were discovered in 11,778- Leber families. The 4,917 and 13,708 mutations appear pathogenetically significant and were observed in 36% (4,917 mutation) and 43% (13,708 mutation) of 11,778- Leber probands. Multiple, simultaneous mutations were noted. Mutation of distinct, functionally related Complex I genes is the central pathogenetic feature of Leber's hereditary optic neuropathy.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: D R
authors.initials: DR
authors.lastname: Johns
authors.forename: J
authors.initials: J
authors.lastname: Berman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016660:NAD(P)H Dehydrogenase (Quinone); D015418:Optic Atrophies, Hereditary / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011808:Quinone Reductases / Q000235:genetics*; D012326:RNA Splicing; D015183:Restriction Mapping
chemical_list: D004272:DNA, Mitochondrial; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases