Exp Mol Med.  2010 Jun;42(6):446-455. 10.3858/emm.2010.42.6.046.

Mutational analysis of whole mitochondrial DNA in patients with MELAS and MERRF diseases

• Choi BO
• Hwang JH
• Cho EM
• Jeong EH
• Hyun YS
• Jeon HJ
• Seong KM
• Cho NS
• Chung KW

• KMID: 1078360
• DOI: http://doi.org/10.3858/emm.2010.42.6.046

Abstract

Mitochondrial diseases are clinically and genetically heterogeneous disorders, which make the exact diagnosis and classification difficult. The purpose of this study was to identify pathogenic mtDNA mutations in 61 Korean unrelated families (or isolated patients) with MELAS or MERRF. In particular, the mtDNA sequences were completely determined for 49 patients. From the mutational analysis of mtDNA obtained from blood, 5 confirmed pathogenic mutations were identified in 17 families, and 4 unreported pathogenically suspected mutations were identified in 4 families. The m.3243A>G in the tRNA(Leu(UUR)) was predominantly observed in 10 MELAS families, and followed by m.8344A>G in the tRNA(Lys) of 4 MERRF families. Most pathogenic mutations showed heteroplasmy, and the rates were considerably different within the familial members. Patients with a higher rate of mutations showed a tendency of having more severe clinical phenotypes, but not in all cases. This study will be helpful for the molecular diagnosis of mitochondrial diseases, as well as establishment of mtDNA database in Koreans.

Keyword

DNA, mitochondrial; MELAS syndrome; MERRF syndrome; point mutation

MeSH Terms

Adolescent
Adult
Amino Acid Sequence
Asian Continental Ancestry Group/genetics
Base Sequence
DNA Mutational Analysis
DNA, Mitochondrial/analysis/*genetics
Female
Humans
MELAS Syndrome/diagnosis/*genetics
MERRF Syndrome/diagnosis/*genetics
Male
Middle Aged
Molecular Diagnostic Techniques
Pedigree
Polymorphism, Single Nucleotide
Sequence Homology
Young Adult