A new mitochondrial disease associated with mitochondrial DNA heteroplasmy.

IJ Holt, AE Harding, RK Petty… - American journal of …, 1990 - ncbi.nlm.nih.gov
IJ Holt, AE Harding, RK Petty, JA Morgan-Hughes
American journal of human genetics, 1990ncbi.nlm.nih.gov
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 …
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.
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