WFS1基因相关遗传性耳聋的研究进展

Research Progress ofWFS1-associated hereditary hearing loss

WFS1基因位于染色体4p16.1,编码一种内质网跨膜Wolfram蛋白,参与调节内质网钙离子的动态平衡,在蛋白质转运和细胞凋亡中发挥重要作用。WFS1基因突变与多种遗传性疾病相关联,存在听力损失症状的类型主要为隐性遗传Wolfram综合征1型、显性遗传的Wolfram相似综合征以及非综合征型低频感音神经性聋(LFSNHL)DFNA6/14/38。Wolfram综合征1型临床表型具有很高的异质性,包括尿崩症、糖尿病、视神经萎缩以及耳聋。Wolfram相似综合征报道很少,与Wolfram综合征1型主要的区别点在于其显性遗传模式。WFS1基因是引起非综合征LFSNHL最常见的致病基因。我们综述WFS1基因关联的遗传性耳聋相关疾病,为临床诊疗提供指导。

The WFS1 gene is located on chromosome 4p16.1 and encodes an endoplasmic reticulum transmembrane Wolfram protein,which is involved in regulating the homeostasis of calcium ions in the endoplasmic reticulum and plays a role in protein transport and apoptosis.Mutations in the WFS1 gene are associated with a variety of hereditary diseases.The main types of hearing loss symptoms are recessive Wolfram syndrome type 1 and dominant Wolframlike syndrome and nonsyndromic low-frequency sensorineural hearing loss(LFSNHL)-DFNA6/14/38.The clinical phenotype of Wolfram syndrome type 1 is highly heterogeneous and includes diabetes insipidus,diabetes,optic atrophy,and deafness.Wolfram-like syndrome is rarely reported,and its'dominant inheritance pattern is distinct from Wolfram syndrome type 1.The WFS1 gene is the most common causative gene for nonsyndromic LFSNHL.This article reviews the hereditary deafness-related diseases associated with the WFS1 gene and provides guidance for clinical diagnosis and treatment.