title: Phenotypic heterogeneity in a Chinese family with mitochondrial disease and A3243G mutation of mitochondrial DNA.
abstract: The A3243G mutation of mitochondrial DNA (mtDNA) has been shown to be responsible for or associated with mitochondrial myopathy, encephalopathy, lactic acidosis, strokelike episodes (MELAS) syndrome, diabetes mellitus (DM) and several other neuromuscular diseases. We used polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) to identify the A3243G mtDNA mutation and an electron microscope to examine mitochondrial derangement in the muscle biopsies of a 38-year-old man suspected to have MELAS syndrome with DM. We found great variability in the clinical presentation and in the proportion of mtDNA with the A3243G mutation in the matrilineal family members of the patient. The proband had atypical MELAS syndrome, recurrent vascular headache, and DM (MELASDM), and his mother manifested chronic progressive ptosis and DM (CPPDM). Brain magnetic resonance imaging of the proband showed high signal intensity in the left temporoparieto-occipital area on T2 weighted images (T2WI). The blood lactate level ranged from 2.32 to 4.70 mmol/l, and two-hour postprandial glucose ranged from 124 mg/dl to 148 mg/dl. The blood lactate and postprandial glucose of the proband's mother were 3.15 mmol/l and 192 mg/dl, respectively. Electron microscopic examination of a muscle biopsy of the patient showed abnormal mitochondria with decreased density of cristae and membrane degeneration. No ragged-red fibers were detected in muscle upon staining with modified Gomori trichrome. The hair follicles and blood cells of the patient and his mother showed the A3243G mutation in the tRNA(Leu)(UUR) gene. The proportions of the mutant DNA in the hair follicles and blood cells of the proband were 36.8% and 35.2%, respectively, and those of the patient's mother were 28.8% and 13.9%, respectively. We conclude that the A3243G mtDNA mutation may manifest with MELASDM or CPPDM in different matrilineal members of the same family as a result of differences in random segregation of the heteroplasmic A3243G mutant mtDNA in the affected tissues of patients.
authors.affiliation: Section of Neurology, Cathay General Hospital, Taipei, Taiwan, ROC.
authors.forename: P
authors.initials: P
authors.lastname: Thajeb
authors.forename: H C
authors.initials: HC
authors.lastname: Lee
authors.forename: C Y
authors.initials: CY
authors.lastname: Pang
authors.forename: C M
authors.initials: CM
authors.lastname: Jeng
authors.forename: S F
authors.initials: SF
authors.lastname: Huang
authors.forename: Y H
authors.initials: YH
authors.lastname: Wei
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics*; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D012356:RNA, Transfer, Leu / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu