title: Leigh disease associated with a novel mitochondrial DNA ND5 mutation.
abstract: Leigh disease is a genetically heterogeneous, neurodegenerative disorder of childhood that is caused by defects of either the nuclear or mitochondrial genome. Here, we report the molecular genetic findings in a patient with neuropathological hallmarks of Leigh disease and complex I deficiency. Direct sequencing of the seven mitochondrial DNA (mtDNA)-encoded complex I (ND) genes revealed a novel missense mutation (T12706C) in the mitochondrial ND5 gene. The mutation is predicted to change an invariant amino acid in a highly conserved transmembrane helix of the mature polypeptide and was heteroplasmic in both skeletal muscle and cultured skin fibroblasts. The association of the T12706C ND5 mutation with a specific biochemical defect involving complex I is highly suggestive of a pathogenic role for this mutation.
authors.affiliation: Department of Neurology, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. r.w.taylor@newcastle.ac.uk
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Andrew A M
authors.initials: AA
authors.lastname: Morris
authors.forename: Michael
authors.initials: M
authors.lastname: Hutchinson
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
mesh_terms: D000328:Adult; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D007888:Leigh Disease / Q000209:etiology / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial