Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation.

Abstract

An A to G transition mutation at nucleotide pair 8344 in human mitochondrial DNA (mtDNA) has been identified as the cause of MERRF. The mutation alters the T psi C loop of the tRNA(Lys) gene and creates a CviJI restriction site, providing a simple molecular diagnostic test for the disease. This mutation was present in three independent MERRF pedigrees and absent in 75 controls, altered a conserved nucleotide, and was heteroplasmic. All MERRF patients and their less-affected maternal relatives had between 2% and 27% wild-type mtDNAs and showed an age-related association between genotype and phenotype. This suggests that a small percentage of normal mtDNAs has a large protective effect on phenotype. This mutation provides molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production.

• Authors: J M Shoffner, M T Lott, A M Lezza, P Seibel, S W Ballinger, D C Wallace
• Journal: Cell (Cell) Vol. 61 Issue 6 Pg. 931-7 (Jun 15 1990) ISSN: 0092-8674 [Print] United States
• PMID: 2112427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Mitochondrial
• Oligonucleotide Probes
• RNA, Transfer, Amino Acid-Specific
• RNA, Transfer, Lys
• Guanine
• Adenine

Topics

• Adenine
• Base Sequence
• DNA, Mitochondrial (genetics)
• Epilepsies, Myoclonic (genetics, pathology)
• Female
• Guanine
• Humans
• Male
• Mitochondria, Muscle (metabolism)
• Molecular Sequence Data
• Mutation
• Nucleic Acid Conformation
• Oligonucleotide Probes
• Pedigree
• RNA, Transfer, Amino Acid-Specific (genetics)
• RNA, Transfer, Lys (genetics)