MELAS: a new disease associated mitochondrial DNA mutation and evidence for further genetic heterogeneity

• Published in: Journal of neurology, neurosurgery and psychiatry neurosurgery and psychiatry, 1998-10, Vol.65 (4), p.512-517
• Main Authors: Hanna, M G, Nelson, I P, Morgan-Hughes, J A, Wood, N W
• Format: Article
• Language: English
• Subjects: Adult; Age; Ataxia; Atrophy; Biological and medical sciences; Biopsy; Convulsions & seizures; Diseases of striated muscles. Neuromuscular diseases; DNA Primers - genetics; DNA, Mitochondrial - genetics; Eye movements; Family medical history; Female; Headaches; Humans; Male; Medical sciences; MELAS; MELAS Syndrome - diagnosis; MELAS Syndrome - genetics; Middle Aged; Mitochondrial DNA; Mutation; Nausea; Neurology; Patients; Phenotype; Phenylalanine - genetics; Plasma; Point Mutation - genetics; Polymerase Chain Reaction - methods; RNA, Transfer, Amino Acid-Specific - genetics; Stroke; Transfer RNA; tRNA gene; Vomiting
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.65.4.512

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.