title: A whole mitochondrial genome screening in a MELAS patient: a novel mitochondrial tRNA(Val) mutation.
abstract: Mitochondrial encephalopathy, lactic acidosis and strokelike episodes (MELAS) syndrome is a mitochondrial disorder characterized by a wide variety of clinical presentations and a multisystemic organ involvement. In this study, we report a Tunisian girl with clinical features of MELAS syndrome who was negative for the common m.3243A>G mutation, but also for the reported mitochondrial DNA (mtDNA) mutations and deletions. Screening of the entire mtDNA genome showed several known mitochondrial variants besides to a novel transition m.1640A>G affecting a wobble adenine in the anticodon stem region of the tRNA(Val). This nucleotide was conserved and it was absent in 150 controls suggesting its pathogenicity. In addition, no mutations were found in the nuclear polymerase gamma-1 gene (POLG1). These results suggest further investigation nuclear genes encoding proteins responsible for stability and structural components of the mtDNA or to the oxidative phosphorylation machinery to explain the phenotypic variability in the studied family.
authors: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia.
authors: Najla
authors: N
authors: Mezghani
authors: Mouna
authors: M
authors: Mnif
authors: Maha
authors: M
authors: Kacem
authors: Emna
authors: E
authors: Mkaouar-Rebai
authors: Ikhlass
authors: I
authors: Hadj Salem
authors: Nozha
authors: N
authors: Kallel
authors: Nadia
authors: N
authors: Charfi
authors: Mohamed
authors: M
authors: Abid
authors: Faiza
authors: F
authors: Fakhfakh
mesh_terms: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005260:Female; D054629:Genome, Mitochondrial / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012366:RNA, Transfer, Val / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D000077278:RNA, Mitochondrial; D012366:RNA, Transfer, Val; D012313:RNA; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human