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Pathogenetic aspects of the A8344G mutation of mitochondrial DNA associated with MERRF syndrome and multiple symmetric lipomas
Author(s) -
Larsson NilsGöran,
Tulinius Mar H.,
Holme Elisabeth,
Oldfors Anders
Publication year - 1995
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.880181421
Subject(s) - mitochondrial dna , mutation , medicine , genetics , biology , pathology , gene
Abstract 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. © 1995 John Wiley & Sons, Inc.