Pathogenetic aspects of the A8344G mutation of mitochondrial DNA associated with MERRF syndrome and multiple symmetric lipomas

✍ Scribed by Dr. Nils-Göran Larsson; Dr. Mar H. Tulinius; Dr. Elisabeth Holme; Dr. Anders Oldfors

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 466 KB
• Volume: 18
• Category: Article
• ISSN: 0148-639X
• DOI: 10.1002/mus.880181421

✦ Synopsis

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.