MELAS: a new disease associated mitochondrial DNA mutation and evidence for further genetic heterogeneity
- Neurogenetics Section, the Department of Clinical Neurology, Institute of Neurology, Queen Square, London, UK
- Dr MG Hanna, Neurogenetics Section, Institute of Neurology, Queen Square, London WCIN 3BG, UK. Telephone 0044 171 837 3611; fax 0044 171 278 5616; emailmhanna{at}ion.ucl.ac.uk
- Received 4 November 1997
- Revised 17 March 1998
- Accepted 19 March 1998
Abstract
OBJECTIVES To define the molecular genetic basis of the MELAS phenotype in five patients without any known mutation of mitochondrial DNA.
METHODS Systematic automated mitochondrial DNA sequencing of all mitochondrial transfer RNA and cytochrome c oxidase genes was undertaken in five patients who had the MELAS phenotype.
RESULTS A novel heteroplasmic mitochondrial DNA mutation was identified in the transfer RNA gene for phenylalanine in one case (patient 3). This mutation was not detected in the patient’s blood or in her mother’s blood. No pathogenic mutations were identified in the other four patients.
CONCLUSIONS This is the first point mutation in the transfer RNA gene for phenylalanine to be associated with MELAS. The absence of mutations in the remaining four patients suggests that there is further genetic heterogeneity associated with this mitochondrial phenotype.
