Department of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA,
Department of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.
Horm Res Paediatr. 2020;93(6):409-414. doi: 10.1159/000510852. Epub 2020 Oct 19.
Wolfram syndrome is a rare neurodegenerative disorder, characterized by the presence of diabetes insipidus, diabetes mellitus, optic atrophy, and sensorineural deafness. The majority of cases are due to autosomal recessive biallelic variants in the WFS1 gene; however, pathogenic autosomal dominant (AD) mutations have also been described. Glucagon-like peptide (GLP-1) agonists have been studied in both animal models and humans with classic Wolfram syndrome.
We present a 15-year-old female with a personal and family history of congenital strabismus, bilateral cataracts, low-frequency sensorineural hearing loss, and diabetes mellitus. Trio whole exome sequencing revealed a previously unknown maternally inherited heterozygous variant in exon 8 of the WFS1 gene c.2605_2616del12 p.Ser869_His872del, leading to the diagnosis of AD WFS1-related disorder. Treatment with a GLP-1 agonist resulted in marked improvement in glycemic control and discontinuation of insulin therapy. This patient's response to a GLP-1 agonist provides suggestive indirect evidence for a role of WFS1 on β-cell endoplasmic reticulum stress and suggests that treatment with a GLP-1 agonist should be considered in patients with dominant forms of WS.
Wolfram 综合征是一种罕见的神经退行性疾病，其特征为存在尿崩症、糖尿病、视神经萎缩和感觉神经性耳聋。大多数病例是由于 WFS1 基因的常染色体隐性双等位基因突变引起的；然而，也已经描述了致病性常染色体显性（AD）突变。胰高血糖素样肽（GLP-1）激动剂已在具有经典 Wolfram 综合征的动物模型和人类中进行了研究。
我们介绍了一位 15 岁的女性，其个人和家族史中有先天性斜视、双侧白内障、低频感觉神经性听力损失和糖尿病。三人全外显子组测序显示 WFS1 基因外显子 8 中的一个先前未知的母系遗传杂合变异 c.2605_2616del12 p.Ser869_His872del，导致 AD WFS1 相关疾病的诊断。GLP-1 激动剂治疗导致血糖控制显著改善，并停止胰岛素治疗。该患者对 GLP-1 激动剂的反应提供了 WFS1 对β细胞内质网应激作用的间接证据，并表明在具有显性形式 WS 的患者中应考虑使用 GLP-1 激动剂进行治疗。
