Heterogeneous presentation in A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene.
OBJECTIVE
To clarify the phenotype-genotype relation associated with the A3243G mitochondrial DNA mutation.


METHODS
Five unrelated probands harbouring the A3243G mutation but presenting different clinical phenotype were analysed. Probands include Leigh syndrome (LS(3243)), mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS(3243)), progressive external ophthalmoplegia (PEO(3243)), and mitochondrial diabetes mellitus (MDM(3243)). Extensive clinical, histological, biochemical, and molecular genetic studies were performed on five families.


RESULTS
All patients showed ragged red fibres (RRF), and focal cytochrome c oxidase (COX) deficiency except for the patient with MDM(3243). The mutation load was highest in the proband with LS(3243) (>90%), who also presented the highest proportion of RRF (68%) and COX negative fibres (10%), and severe complex I plus IV deficiency. These proportions were lower in the probands with PEO(3243) and with MDM(3243).


CONCLUSIONS
The most severe clinical phenotype, LS(3243), was associated with the highest proportion of the A3243G mutation as well as the most prominent histological and biochemical abnormalities.
Koga
Y
Y
Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi Machi, Kurume City, Fukuoka 830-0011, Japan. yasukoga@med.kurume-u.ac.jp
Akita
Y
Y
Takane
N
N
Sato
Y
Y
Kato
H
H
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000201:enzymology / Q000235:genetics; D017241:MELAS Syndrome / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology / Q000235:genetics; D017240:Mitochondrial Myopathies / Q000201:enzymology / Q000235:genetics; D008967:Molecular Biology; D009154:Mutation / Q000235:genetics*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000201:enzymology / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000235:genetics*
D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D012313:RNA; D012343:RNA, Transfer