Phenotypes and mitochondrial DNA substitutions in families with A3243G mutation.

OBJECTIVE

To clarify the relationship between mitochondrial DNA (mtDNA) sequence variations and phenotypes in patients with A3243G mutation.

MATERIALS AND

METHODS

We studied whole mtDNA sequences in two families with A3243G mutation and characteristic clinical features. Two brothers in Family 1 had shown thiamine deficiency and mitochondrial myopathy without central nervous system involvement. In Family 2, a 16-year-old woman showed the symptoms of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Her mother had had diabetes mellitus and died at the age of 42. The proportion of A3243G mtDNA in blood was 87 and 89% in the patients of Family 1, and 25% in the patient and less than 5% in the mother of Family 2.

RESULTS

The mtDNA analysis revealed the following homoplasmic substitutions: T1520C and C12153T found only in Family 1, and A15954G found only in Family 2. These substitutions were not detected in seven other MELAS patients or in 50 controls.

CONCLUSION

These substitutions might be specific to these families and could be one of the factors that modulate their clinical features together with the A3243G mutation.