title: A new mitochondrial disease associated with mitochondrial DNA heteroplasmy.
abstract: A variable combination of developmental delay, retinitis pigmentosa, dementia, seizures, ataxia, proximal neurogenic muscle weakness, and sensory neuropathy occurred in four members of a family and was maternally transmitted. There was no histochemical evidence of mitochondrial myopathy. Blood and muscle from the patients contained two populations of mitochondrial DNA, one of which had a previously unreported restriction site for AvaI. Sequence analysis showed that this was due to a point mutation at nucleotide 8993, resulting in an amino acid change from a highly conserved leucine to arginine in subunit 6 of mitochondrial H(+)-ATPase. There was some correlation between clinical severity and the amount of mutant mitochondrial DNA in the patients; this was present in only small quantities in the blood of healthy elderly relatives in the same maternal line.
authors: University Department of Clinical Neurology, Institute of Neurology, London, England.
authors: I J
authors: IJ
authors: Holt
authors: A E
authors: AE
authors: Harding
authors: R K
authors: RK
authors: Petty
authors: J A
authors: JA
authors: Morgan-Hughes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D006180:Proton-Translocating ATPases / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: D000596:Amino Acids; D004272:DNA, Mitochondrial; C028678:CYCGRG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; D006180:Proton-Translocating ATPases