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A new mutation associated with MELAS is located in a mitochondrial DNA polypeptide-coding gene
G Manfredi1, E A Schon, C T Moraes
1H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Disorders, New York, USA.
Neuromuscular Disorders : NMD
|September 1, 1995
Summary
Researchers identified a new mitochondrial DNA mutation in the COX III gene causing MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). This finding expands the known genetic causes of MELAS beyond tRNA genes.
Area of Science:
- Genetics
- Mitochondrial Biology
- Neurology
Background:
- Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe maternally inherited disorder.
- Mutations in mitochondrial DNA (mtDNA)-encoded tRNA genes are the most common cause of MELAS.
- The genetic basis for some MELAS cases remains unexplained.
Observation:
- A patient with MELAS presented with a novel missense mutation (T9957C) in the mtDNA-encoded COX III gene.
- This mutation altered a conserved phenylalanine residue (Phe-251) to leucine in the cytochrome c oxidase subunit III polypeptide.
- The mutation was heteroplasmic in the patient's muscle and blood, and also detected in the blood of his asymptomatic mother.
Findings:
- The identified T9957C mutation in the COX III gene was absent in 107 healthy controls and 57 patients with other mitochondrial diseases.
- This novel mutation provides direct evidence linking a defect in a polypeptide-coding mtDNA gene to the MELAS phenotype.
- Heteroplasmy suggests varying levels of mutant mtDNA contribute to disease severity.
Implications:
- The findings broaden the spectrum of genetic defects associated with MELAS, including mutations in protein-coding genes.
- This expands diagnostic possibilities for MELAS patients with unknown genetic causes.
- Understanding mutations in COX III may offer new therapeutic targets for MELAS and related mitochondrial disorders.