A novel G3337A mitochondrial ND1 mutation related to cardiomyopathy co-segregates with tRNA(Leu(CUN)) A12308G and tRNA(Thr) C15946T mutations

We describe a novel Mutation in human mitochondrial NADH dehydrogenase 1 gene (ND1), a G to A transition at nucleotide position 3337,which is co-segregated with two known mutations in tRNA(Leu(CUN)) A12308G and tRNA(Thr) C15946T. These mutations were detected in two unrelated patients with different clinical phenotypes, exhibiting cardiomyopathy as the common symptom. The ND1 G3337A mutation that was detected was found almost homoplasmic in the two patients and it was absent in 150 individuals that were tested as control group. Mitochondrial respiratory chain complex I activity of the patients platelets was also tested and found decreased compared to those of controls. We suggest that the co-existence of mutations in tRNA and ND1 genes may act synergistically affecting the clinical phenotype. Our study highlights the enormous phenotypic diversity that exists among pathogenic mtDNA mutations and re-emphasizes the need for a more careful clinical approach. (c) 2008 Elsevier B.V. and Mitochondria Research Society. All rights reserved