Mutational analysis of whole mitochondrial DNA in patients with MELAS and MERRF diseases.
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.
Choi
Byung-Ok
BO
Department of Neurology, Ewha Womans University, School of Medicine, Ewha Medical Research Institute, Seoul, Korea.
Hwang
Jung Hee
JH
Cho
Eun Min
EM
Jeong
Eun Hye
EH
Hyun
Young Se
YS
Jeon
Hyeon Jeong
HJ
Seong
Ki Min
KM
Cho
Nam Soo
NS
Chung
Ki Wha
KW
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D005260:Female; D006801:Humans; D017241:MELAS Syndrome / Q000175:diagnosis / Q000235:genetics*; D017243:MERRF Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017385:Sequence Homology; D055815:Young Adult
D004272:DNA, Mitochondrial