title: A novel G3337A mitochondrial ND1 mutation related to cardiomyopathy co-segregates with tRNALeu(CUN) A12308G and tRNAThr C15946T mutations.
abstract: 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 tRNALeu(CUN) A12308G and tRNAThr 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.
authors.affiliation: Department of Biochemistry & Biotechnology, University of Thessaly, 26 Ploutonos Street, 41221 Larissa, Greece.
authors.forename: Emily
authors.initials: E
authors.lastname: Zifa
authors.forename: Paschalis
authors.initials: P
authors.lastname: Theotokis
authors.forename: Archontia
authors.initials: A
authors.lastname: Kaminari
authors.forename: Helen
authors.initials: H
authors.lastname: Maridaki
authors.forename: Helen
authors.initials: H
authors.lastname: Leze
authors.forename: Efrosini
authors.initials: E
authors.lastname: Petsiava
authors.forename: Zissis
authors.initials: Z
authors.lastname: Mamuris
authors.forename: Constantinos
authors.initials: C
authors.lastname: Stathopoulos
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D009202:Cardiomyopathies / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008715:Methionine / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D009245:NADH Dehydrogenase / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D017433:Protein Structure, Secondary; D012356:RNA, Transfer, Leu / Q000235:genetics*; D012363:RNA, Transfer, Thr / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I; D008715:Methionine; D009245:NADH Dehydrogenase; D012356:RNA, Transfer, Leu; D012363:RNA, Transfer, Thr; C515075:NADH dehydrogenase subunit 1, human