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.

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.

Conclusions: 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.