Did de novo MELAS common mitochondrial DNA point mutation (mtDNA 3243, A → G transition) occur in the mother of a proband of a Japanese MELAS pedigree?

Abstract

MELAS is a major maternally inherited mitochondrial (mt) encephalomyopathy of which 80% of cases are associated with mtDNA point mutation (mtDNA 3243, A → G transition) which exists under heteroplasmic conditions with wild-type mtDNA. The origin of this mutation remains obscure in the reported pedigrees. I analyzed this mutation in a Japanese MELAS pedigree by PCR. The proband had typical MELAS features. The proband's mother was oligosymptomatic (fatigability, nerve deafness and diabetes mellitus). The proband's maternal grandmother was diagnosed as having senile dementia of the Alzheimer type clinically. The brother of the proband's mother was healthy. The ratios of this mutation in muscle and leukocytes of the proband and his mother were 89%, 36%, 79% and 10%, respectively. There were no mutations in muscle and leukocytes of the proband's maternal grandmother and his mother's brother. These results showed the possibility that this mutation occurred in the proband's mother.