Heteroplasmy and phenotype spectrum of the mitochondrial tRNALeu (UUR) gene m.3243A>G mutation in seven Han Chinese families.

The m.3243A > G mutation in the mitochondrial tRNALeu (UUR) gene is associated with a variety of phenotypic heterogeneity. The clinical spectrum and phenotypic-genotypic correlations in the Chinese patients are poorly understood. In the present study, we reported the clinical and genetic characterization, as well as haplogroups of seven Han Chinese families carrying the m.3243A > G mutation. Of the 39 matrilineal individuals, five suffered from mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), two had life-threatening mitochondrial myopathy (LTMM), and one patient had neuropathy, ataxia, and retinitis pigmentosa (NARP)-like syndrome. The LTMM and NARP like syndromes enriched the phenotypic profile of the m.3243A > G mutation. The heteroplasmy of the m.3243A > G mutation ranged from 16% to 59% in MELAS, 29% to 79% in LTMM, and 57% in a NARP-like syndrome patient. The levels ranged from 0% to 14% in patients that manifested with pure diabetes and pure hearing loss, and 0% to 5% in 13 normal family members. However, we particularly noticed heteroplasmy in four asymptomatic individuals in one LTMM family carried the heteroplasmy mutation ranged from 22% to 78%, implying that there were other modifying factors in this family. The modulation of the phenotype of mtDNA mutations requires further investigation.