A novel mitochondrial DNA tRNAIle (m.4322dupC) mutation associated with idiopathic dilated cardiomyopathy.
We identified a novel heteroplasmic mitochondrial DNA (mtDNA) (m.4322dupC) mutation in tRNA gene associated with isolated dilated cardiomyopathy (DCM) as maternal trait. Mutation screening techniques and automated DNA sequencing were performed to identify mtDNA mutations and to assess heteroplasmy in family's proband and healthy control subjects. All family members tested had heteroplasmic mtDNA m.4322dupC mutation. We also screened 350 normal controls for this mutation and found no evidence of heteroplasmy. The m.4322dupC mutation was found in the skeletal tissue from the proband that exhibited slightly reduced deficiency of mitochondrial respiratory chain enzymes (complex III). The present study reports the novel m.4322dupC mutation in tRNA gene, which is possibly associated to the disease, to isolated DCM. It was localized in a hot-spot region for mutations and is possibly pathogenic because of a cosegregation with the matrilineal transmission of DCM.
Unité d'Epidémiologie Génétique et Moléculaire. Faculté de Médecine de Tunis, Tunisie.
Sinda
S
Mahjoub
Damien
D
Sternberg
Rafik
R
Boussaada
Sandrine
S
Filaut
Fathi
F
Gmira
Rachid
R
Mechmech
Claude
C
Jardel
Saïda Ben
SB
Arab
D000328:Adult; D000595:Amino Acid Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012355:RNA, Transfer, Ile / Q000235:genetics*
D004272:DNA, Mitochondrial; D012355:RNA, Transfer, Ile