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Identification of a novel mutation in the mtDNA ND5 gene associated with MELAS
F M Santorelli1, K Tanji, R Kulikova
1Department of Neurology, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
Abstract:
We report a novel G13513A mutation in the mitochondrial ND5 gene in a patient who had morphologically and biochemically abnormal muscle mitochondria and died at age 45 with a diagnosis of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). The mutation affects an evolutionarily conserved nucleotide and was heteroplasmic in muscle, leukocytes, and several autopsy tissues, including brain. The mutation was less abundant (<5%) in leukocytes from an asymptomatic sister and was not found in over 100 controls, thus satisfying accepted criteria for pathogenicity. Our report reinforces the concept of genetic heterogeneity in MELAS and confirms that MELAS can be due to mutations in polypeptide-coding mtDNA genes.
Insights
A new mitochondrial DNA mutation, G13513A in the ND5 gene, caused MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) in a patient. This finding highlights genetic diversity in MELAS causes.
Area of Science:
- Genetics
- Mitochondrial Biology
- Neurology
Background:
- MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a complex mitochondrial disorder.
- Genetic heterogeneity is recognized in MELAS, but specific mutations in mtDNA polypeptide-coding genes are still being identified.
Observation:
- A patient diagnosed with MELAS exhibited abnormal muscle mitochondria morphologically and biochemically.
- This patient carried a novel G13513A mutation in the mitochondrial ND5 gene.
Findings:
- The G13513A mutation was heteroplasmic across multiple tissues, including brain, muscle, and leukocytes.
- The mutation was absent in over 100 controls and present at low levels in an asymptomatic sister, supporting its pathogenicity.
- The mutation affects an evolutionarily conserved nucleotide within the ND5 gene.
Implications:
- This discovery expands the known genetic causes of MELAS.
- It confirms that mutations in mtDNA polypeptide-coding genes can lead to MELAS.
- The findings underscore the importance of investigating mtDNA for novel mutations in MELAS patients.