Novel missense mitochondrial DNA 4079A>G variation in familial early-onset Parkinson’s disease

Abstract

Background

Familial Parkinson's Disease (familial PD) and Early-Onset Parkinson's Disease (EOPD) are both uncommon disorders. Genetic analyses of familial EOPD have been limited due to its rarity. Here, we report four members of a family with familial EOPD carrying a novel mtDNA variation.

Case report

Four members of a family presenting with bradykinesia, muscular rigidity and resting tremor were diagnosed as having familial EOPD. The patients’ peripheral blood was analyzed for the presence of three previously known mtDNA variations in PD, viz m.4216T>C, m.4917A>G, and m.15928G>A using PCR-RFLP; none of these variants were identified in the four patients. However, we found a novel mtDNA m.4079A>G variation in ND1 (NADH dehydrogenase 1) gene in all the tested four family members.

Discussion

The m.4079A>G is a missense variation giving rise to a Tyr-Cys aminoacid substitution in ND1 protein (ND1:p.Tyr258Cys). This may lead to a defective protein influencing oxidative phosphorylation. Therefore, wider analyses of mRNA expression, protein transcription, and functional neuroimaging of brain energy metabolism are required in EOPD patients.