Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia.
Biochem Biophys Res Commun. 2011 Jul 29;411(2):247-52. doi: 10.1016/j.bbrc.2011.06.106. Epub 2011 Jun 23.
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.
Wolfram 综合征（WFS）是一种罕见的遗传性疾病，也称为 DIDMOAD（尿崩症、糖尿病、视神经萎缩和耳聋）。它是一种异质性疾病，很难全面描述这种疾病的所有临床和生物学特征。其临床表现广泛，影响多个器官和组织，且 Wolfram 综合征患者与某些类型的呼吸链疾病患者的表型相似，这提示线粒体 DNA（mtDNA）参与了 Wolfram 综合征患者的发病机制。我们报告了一名突尼斯患者，其临床特征为中度 Wolfram 综合征，包括糖尿病、扩张型心肌病和神经并发症。结果显示，在先证者的 3 种检测组织（外周血白细胞、口腔黏膜和骨骼肌）中，存在线粒体 ND1 m.3337G>A 突变，几乎呈同质形式。此外，长距离 PCR 扩增显示，从患者骨骼肌中提取的线粒体 DNA 存在多个缺失，去除了几个 tRNA 和蛋白质编码基因。我们的研究报告了一名突尼斯患者，其临床特征为中度 Wolfram 综合征，伴发心肌病，我们检测到了 ND1 m.3337G>A 突变和线粒体的多个缺失。
