title: The mitochondrial ND1 m.3337G>A mutation associated to multiple mitochondrial DNA deletions in a patient with Wolfram syndrome and cardiomyopathy.
abstract: Wolfram syndrome (WFS) is a rare hereditary disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). It is a heterogeneous disease and full characterization of all clinical and biological features of this disorder is difficult. The wide spectrum of clinical expression, affecting several organs and tissues, and the similarity in phenotype between patients with Wolfram syndrome and those with certain types of respiratory chain diseases suggests mitochondrial DNA (mtDNA) involvement in Wolfram syndrome patients. We report a Tunisian patient with clinical features of moderate Wolfram syndrome including diabetes, dilated cardiomyopathy and neurological complications. The results showed the presence of the mitochondrial ND1 m.3337G>A mutation in almost homoplasmic form in 3 tested tissues of the proband (blood leukocytes, buccal mucosa and skeletal muscle). In addition, the long-range PCR amplifications revealed the presence of multiple deletions of the mitochondrial DNA extracted from the patient's skeletal muscle removing several tRNA and protein-coding genes. Our study reported a Tunisian patient with clinical features of moderate Wolfram syndrome associated with cardiomyopathy, in whom we detected the ND1 m.3337G>A mutation with mitochondrial multiple deletions.
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: Emna
authors: E
authors: Mkaouar-Rebai
authors: Nozha
authors: N
authors: Kallel
authors: Ikhlass Haj
authors: IH
authors: Salem
authors: Nadia
authors: N
authors: Charfi
authors: Mohamed
authors: M
authors: Abid
authors: Faiza
authors: F
authors: Fakhfakh
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D009202:Cardiomyopathies / Q000150:complications / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D017384:Sequence Deletion; D014929:Wolfram Syndrome / Q000150:complications / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human