Parkinson disease: analysis of mitochondrial DNA in monozygotic twins

We have sequenced all mitochondrial complex I and tRNA genes in five pairs of monozygotic twins with a longitudinal diagnosis of idiopathic Parkinson disease (PD). At the time of molecular genetic analysis, four of the pairs were discordant for PD. Five novel homoplasmic sequence variants, including two missense mutations (ND2 4924 G/A, ND3 10192 C/T), were detected in mitochondrial genes of complex I in four of the pairs. In addition, a total of 20 known polymorphisms affecting both complex I and tRNA genes was found. Importantly, mitochondrial DNA sequences were identical in diseased and non-affected siblings of each pair. Our results demonstrate that missense mutations of mitochondrial complex I may occur in clinically discordant parkinsonian twins, questioning the direct pathogenic relevance of at least some of these mutations.