Mitochondrial genetic analysis in a Chinese family suffering from both mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes and diabetes

Abstract

To investigate the mitochondrial mutations in patients suffering from both mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) and maternally inherited diabetes. MELAS was confirmed by muscle biopsy performed from the biceps muscle of the proband. Mitochondrial DNA (mtDNA) was isolated from peripheral blood mononuclear cells. The significant mtDNA loci of other 14 family members were further detected according to the sequencing results of the proband. Direct sequencing of PCR products was used to identify the mitochondrial mutations. The proband (III 1) and her brother (III 3) both harbored the tRNALeu (UUR) A3243G mutation, with heteroplasmic levels of 50% and 33% respectively. Moreover, another two mitochondrial variants, A8860G and A15326G, were also detected in the samples of all the family members. MELAS and diabetes can coexist in one patient, and the main cause for these diseases is the tRNALeu (UUR) A3243G mutation. However, other gene variants may contribute to its pathogenesis. This case also supports the concept that both syndromes can be regarded as two phenotypes of the same disease.

Keywords: A3243G mutation; Diabetes; MELAS; heteroplasmy; mitochondrial myopathy; polymorphism.

Figure 1

Pedigree of the family with diabetes and seizures. Arrow marks the proband.

Figure 2

The muscle pathological staining of the proband.

Figure 3

The mitochondrial tRNALeu (UUR) A3243G mutation is present in the proband and her brother (III 1 and III 3), but not found in other maternal members. Arrows indicate nucleotide position 3243.