Tanabe Katsuya, Matsunaga Kimie, Hatanaka Masayuki, Akiyama Masaru, Tanizawa Yukio
Nihon Rinsho. 2015 Feb;73(2):341-9.
Wolfram syndrome(WFS: OMIM 222300) is a rare recessive neuro-endocrine degenerative disorder, known as DIDMOAD(Diabetes Insipidus, early-onset Diabetes Mellitus, Optic Atrophy and Deafness) syndrome. Most affected individuals carry recessive mutations in the Wolfram syndrome 1 gene(WFS1). The WFS1 protein is an endoplasmic reticulum(ER) embedded protein, which functions in ER calcium homeostasis and unfolded protein responses. Dysregulation of these cellular processes results in the development of ER stress, leading to apoptosis. In addition, abundantly present WFS1 protein in insulin secretory granules plays a role in the intra-granular acidification. However, the phenotypic pleiomorphism and molecular complexity of this disease limit the understanding of WFS. Here we review clinical features, molecular mechanisms and mutations of WFS1 gene that relate to this syndrome.
沃夫勒姆综合征（WFS：OMIM 222300）是一种罕见的隐性神经内分泌退行性疾病，被称为尿崩症、早发型糖尿病、视神经萎缩和耳聋（DIDMOAD）综合征。大多数患者在沃夫勒姆综合征1基因（WFS1）中携带隐性突变。WFS1蛋白是一种内质网（ER）嵌入蛋白，在ER钙稳态和未折叠蛋白反应中发挥作用。这些细胞过程的失调会导致ER应激的发展，进而导致细胞凋亡。此外，胰岛素分泌颗粒中大量存在的WFS1蛋白在颗粒内酸化中起作用。然而，这种疾病的表型多态性和分子复杂性限制了对WFS的理解。在此，我们综述了与该综合征相关的WFS1基因的临床特征、分子机制和突变。
