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: Najla Mezghani, Mouna Mnif, Emna Mkaouar-Rebai, Nozha Kallel, Ikhlass Haj Salem, Nadia Charfi, Mohamed Abid, Faiza Fakhfakh
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 411 Issue 2 Pg. 247-52 (Jul 29 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 21723259 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• DNA, Mitochondrial
• NADH Dehydrogenase
• NADH dehydrogenase subunit 1, human

Topics

• Adult
• Amino Acid Sequence
• Cardiomyopathies (complications, genetics)
• DNA, Mitochondrial (genetics)
• Humans
• Male
• Mitochondria (enzymology, genetics)
• Molecular Sequence Data
• Mutation
• NADH Dehydrogenase (genetics)
• Sequence Deletion
• Wolfram Syndrome (complications, genetics)