Usher综合征与USH2A基因的研究进展

Usher综合征(USH)是一种以先天性感音神经性聋和视觉功能进行性丧失为特征的遗传性疾病,具有高度的遗传异质性及临床异质性,目前尚无有效的预防和治愈方法。目前已知USH有14个致病基因,USH2A突变是其最常见的原因。随着对USH2A基因研究的深入,USH2A致病机制、动物模型建立、临床诊断以及基于基因治疗、细胞移植和RNA剪接的治疗等方面研究皆取得了巨大进展。如,USH2A的突变导致参与外周纤毛区运输功能的USH复合体蛋白产生缺陷;基于此致病机制的小鼠及斑马鱼动物模型被建立,但存在其各自局限性;通过成簇规律间隔的短回文重复序列及其相关蛋白9系统对患者来源诱导多功能干细胞进行纠正后,将其诱导为视器官以进行临床的功能纠正性移植和基于反义寡核苷酸的RNA剪接治疗在此病的治疗中属于前景性研究。

Advances of Usher syndrome and USH2A gene

Usher syndrome(USH)is the most common cause of deaf-blindness diseases characterized by sensorineural hearing loss and retinitis pigmentosa.Patients are clinically and genetically heterogeneous,however,there are no convincing methods for prevention and treatment.USH2A is the most common disease-causing gene among 14 genes related to Usher syndrome.Great progress has been achieved in the pathogenic mechanism,animal models studies,diagnosis,and treatments based on gene therapy,cells transplantation and antisense oligonucleotide-based splice correction.Mutations in USH2A result in defects in USH complex proteins which involved in the transport function of the peripheral cilia region.There is respective limitations in established mouse and zebrafish animal models.Two promising treatments of this disease are introduced.One is clinical transplantation of visual organs which induced from corrected patient-derived induced pluripotent stem cells by the CRISPR/Cas9 system and another one is the RNA splicing therapy based on antisense oligonucleotides.