MELAS: a new disease associated mitochondrial DNA mutation and evidence for further genetic heterogeneity.
OBJECTIVE
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.
Hanna
M G
MG
Department of Clinical Neurology, Institute of Neurology, London, UK. mhanna@ion.ucl.ac.uk
Nelson
I P
IP
Morgan-Hughes
J A
JA
Wood
N W
NW
D000328:Adult; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D017241:MELAS Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010649:Phenylalanine / Q000235:genetics; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics
D017931:DNA Primers; D004272:DNA, Mitochondrial; D012345:RNA, Transfer, Amino Acid-Specific; D010649:Phenylalanine