Abstract：
Background: Wolfram syndrome (WFS) is an autosomal recessive disorder that often leads to diabetes, optic atrophy, and sensorineural hearing loss. The aim of this study was to determine the clinical characteristics and the genetic cause of the first two Moroccan families presenting with WFS. Methods: The clinical features of five members of two WFS families were evaluated. Whole-exome sequencing was conducted to explore the underlying genetic cause in the affected patients. Results: Two homozygous variants in the WFS1 gene were identified, each in one of the two families studied: a missense c.1329C>G variant (p.Ser443Arg) and a nonsense mutation c.1113G>A (p.Trp371Ter). These variants affected conserved amino acid residues, segregated well in the two families, and are absent from genetic databases and in controls of Moroccan origin. Bioinformatics analysis classified the two variants as pathogenic by in silico tools and molecular modeling. Conclusion: Our study identified for the first time two variants in Moroccan patients with WFS that extends the mutational spectrum associated with the disease.
摘要：
背景：Wolfram综合征（WFS）是一种常染色体隐性遗传疾病，通常会导致糖尿病，视神经萎缩,和感觉神经性听力损失。这项研究的目的是确定出现WFS的前两个摩洛哥家庭的临床特征和遗传原因。方法：对两个WFS家族的5名成员的临床特征进行评估。进行全外显子组测序以探索受影响患者的潜在遗传原因。结果：在WFS1基因中鉴定出两个纯合变异体，每个都在研究的两个家庭之一中：错义c.1329C>G变体（p。Ser443Arg）和无义突变c.1113G>A（p。Trp371Ter）。这些变体影响保守的氨基酸残基，在这两个家庭中隔离良好，并且不存在于遗传数据库和摩洛哥血统的对照中。生物信息学分析通过计算机模拟工具和分子建模将这两种变体分类为致病性。结论：我们的研究首次在摩洛哥WFS患者中发现了两个变体，这些变体扩展了与该疾病相关的突变谱。
