Pathogenetic aspects of the A8344G mutation of mitochondrial DNA associated with MERRF syndrome and multiple symmetric lipomas.
Myoclonus epilepsy and ragged-red fibers syndrome (MERRF) is caused by a heteroplasmic mutation at nucleotide 8344 (A8344G) of the tRNA(Lys) gene of mitochondrial DNA (mtDNA). This mutation impairs mitochondrial protein synthesis and causes a respiratory chain dysfunction. The risk for transmission of the A8344G mutation from mother to child is dependent on the levels of mutated mtDNA in the mother and above a threshold level of 35-40% the mutation is transmitted to all children. The progression of symptoms in MERRF can be explained by a gene dosage effect with accumulation over time of mutated mtDNA. High levels of mutated mtDNA, ultrastructurally abnormal mitochondria, and a clonal deletion on chromosome 6 are found in lipomas associated with MERRF. These findings indicate that there is a respiratory chain dysfunction in the lipomas and that lipomas may be a manifestation of the A8344G mutation.
Larsson
N G
NG
Department of Developmental Biology, Stanford University School of Medicine, CA 94305-5427, USA.
Tulinius
M H
MH
Holme
E
E
Oldfors
A
A
D002648:Child; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008067:Lipoma / Q000235:genetics*; D017243:MERRF Syndrome / Q000235:genetics* / Q000378:metabolism; D009035:Mothers; D009154:Mutation; D010766:Phosphorylation; D012357:RNA, Transfer, Lys / Q000235:genetics
D004272:DNA, Mitochondrial; D012357:RNA, Transfer, Lys