Figure 5.
MERRF tRNALys A8344G pedigree showing variable clinical expression in association with variable mtDNA mutant heteroplasmy modified by age. (A) Structure of tRNALys showing position of A8344G transition in TΨC loop. (B) Pedigree of proband (III-1) showing that all maternal relatives had some clinical manifestations (filled symbols), though highly variable, while the three paternal sons were symptom free. VER, visual evoked response; EEG, electroencephalograph; Mito. myop., mitochondrial myopathy with ragged red fibers and abnormal mitochondria; deafness, sensory neural hearing loss; ME, myoclonic epilepsy; dementia, progressive cognitive decline; hypovent, hypoventilation. (C) Pedigree showing variable proportions of mutant-type (mt) and wild-type (wt) mtDNA along the maternal pedigree. A 183-nt PCR fragment was digested with CviJI. The wild-type (8344A) gave an 88-nt uncut fragment, whereas the mutant (8344G) created a new site cutting the 88-nt fragment into 48 and 40 nt fragments. “CL” is a cloned mutant fragment. Cases (A), (B), and (C) are independent pedigrees. Individual (C) is the maternal aunt of proband III-1 in (A), which manifested MERRF. All of the maternal relatives of the pedigree are heteroplasmic for the mutant mtDNA and the severity of the phenotype correlated with the percentage of heteroplasmy when corrected for age. (From Wallace et al. 1988b; reproduced, with permission, from the author and from Shoffner et al. 1990; reproduced, with permission, from the author and the National Academy of Sciences © 1990.)