BACKGROUND Mutations of the WFS1 gene are responsible for most cases of Wolfram syndrome (WS), a rare, recessively inherited neurodegenerative disorder characterized by juvenile-onset non-autoimmune diabetes mellitus and optic atrophy. Variants of WFS1 are also associated with non-syndromic hearing loss and type-2 diabetes mellitus (T2DM). Our study adds to literature significant associations between WS and T2DM. CASE PRESENTATION In this study, we analyzed the clinical and genetic data of two families with high prevalence of WS and T2DM. Genetic linkage analysis and DNA sequencing were exploited to identify pathogenic variants. One novel pathogenic variant (c.2243-2244insC) and one known pathogenic (c.1232_1233delCT) (frameshift) variant were identified in exon eight of WFS1 gene. CONCLUSIONS The mutational and phenotypic spectrum of WS is broadened by our report of novel WFS1 mutation. Our results reveal the value of molecular analysis of WFS1 in the improvement of clinical diagnostics for WS. This study also confirms the role of WFS1 in T2DM.

中文翻译：

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两个高发病率的Wolfram综合征和II型糖尿病的两个Wolfram综合征家族的临床和遗传分析：一例报告。

背景WFS1基因的突变是导致Wolfram综合征（WS）的大多数病例的原因，Wolfram综合征是一种罕见的，隐性遗传性神经退行性疾病，其特征是少年发作的非自身免疫性糖尿病和视神经萎缩。WFS1的变体还与非综合征性听力损失和2型糖尿病（T2DM）相关。我们的研究为WS和T2DM之间增加了重要的联系。病例表述在本研究中，我们分析了WS和T2DM患病率较高的两个家族的临床和遗传数据。利用遗传连锁分析和DNA测序来鉴定致病变体。在WFS1基因的第8外显子中鉴定出一种新的致病变异（c.2243-2244insC）和一种已知的致病变异（c.1232_1233delCT）（移码）。结论WS的突变和表型谱被我们关于新型WFS1突变的报道拓宽了。我们的结果揭示了WFS1分子分析在改善WS临床诊断中的价值。这项研究还证实了WFS1在T2DM中的作用。