In a 29-year-old man with adult-onset progressive muscle weakness with exercise intolerance and diabetes mellitus (500002), Hao et al. (1995) identified a 14709T-C transition in the MTTE gene, which altered an evolutionarily conserved nucleotide in the region specifying for the anticodon loop of mitochondrial tRNA (glu). The 14709T-C mutation was heteroplasmic, but present at very high levels in the patient's muscle, white blood cells, and hair follicles; lower proportions of mutated mtDNA were observed in white blood cells and hair follicles of all examined maternal relatives.
Hanna et al. (1995) reported a family in which the 14709T-C mutation had different phenotypic associations, including congenital myopathy, mental retardation, cerebellar ataxia, and diabetes mellitus.
In an extensively studied family with myopathy and diabetes mellitus originally reported by Hudgson et al. (1972), McFarland et al. (2004) identified the 14709T-C mutation. The mutation was homoplasmic in almost all tissues from the most severely affected patient and in the muscle tissue from another affected family member. Other members had high percentages of heteroplasmy (80 to 94% mutant load). One asymptomatic family member was homoplasmic for the mutation in white blood cells.
Vialettes et al. (1997) identified the 14709T-C mutation in a proband with adult-onset IDDM and severe myopathy. The patient was also found to have a subclinical hearing impairment of high frequencies, suggesting maternally inherited diabetes and deafness (MIDD; 520000). Mild retinal pigmentary epithelial changes were also detected. In 1 branch of the family, however, the mutation was transmitted through 3 generations without clinical expression of diabetes, retinopathy, deafness, or myopathy. Perucca-Lostanlen et al. (2002) performed in vitro studies of the 14709T-C mutation derived from the patient reported by Vialettes et al. (1997). A subtle decrease in steady-state levels of the mRNA transcripts was detected, but there was no difference in mitochondrial respiratory chain enzymatic activities compared to wildtype. Perucca-Lostanlen et al. (2002) suggested that additional nuclear factors may be involved in expression of the phenotype.
Damore et al. (1999) identified the 14709T-C mutation in a mother and son with mitochondrial myopathy and diabetes mellitus. The case was unusual in that the son had early onset of diabetes mellitus at age 8 years, whereas the mother was diagnosed at age 25 years.
Rigoli et al. (2001) reported a family with the 14709T-C mutation in which affected members had a variable phenotype, including MIDD, diabetes, deafness, and myopathy. Age at onset varied, but 3 patients had onset of symptoms in childhood.
