Molecular, Cellular and Genomics Biomedicine Research Group, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain.
Unidad Mixta de Enfermedades Raras IIS La Fe-Centro de Investigación Príncipe Felipe, 46026 Valencia, Spain.
Int J Mol Sci. 2021 Jun 23;22(13):6723. doi: 10.3390/ijms22136723.
Usher syndrome (USH) is an autosomal recessive syndromic ciliopathy characterized by sensorineural hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. There are three clinical types depending on the severity and age of onset of the symptoms; in addition, ten genes are reported to be causative of USH, and six more related to the disease. These genes encode proteins of a diverse nature, which interact and form a dynamic protein network called the "Usher interactome". In the organ of Corti, the USH proteins are essential for the correct development and maintenance of the structure and cohesion of the stereocilia. In the retina, the USH protein network is principally located in the periciliary region of the photoreceptors, and plays an important role in the maintenance of the periciliary structure and the trafficking of molecules between the inner and the outer segments of photoreceptors. Even though some genes are clearly involved in the syndrome, others are controversial. Moreover, expression of some USH genes has been detected in other tissues, which could explain their involvement in additional mild comorbidities. In this paper, we review the genetics of Usher syndrome and the spectrum of mutations in USH genes. The aim is to identify possible mutation associations with the disease and provide an updated genotype-phenotype correlation.
Usher 综合征（USH）是一种常染色体隐性综合征性纤毛病，其特征是感觉神经性听力损失、视网膜色素变性，有时还伴有前庭功能障碍。根据症状的严重程度和发病年龄，该病有三种临床类型；此外，有 10 个基因被报道与 USH 有关，还有 6 个与该病相关。这些基因编码具有不同性质的蛋白质，它们相互作用并形成一个称为“Usher 相互作用组”的动态蛋白质网络。在耳蜗中，USH 蛋白对于毛细胞的正确发育和结构以及纤毛的黏附至关重要。在视网膜中，USH 蛋白网络主要位于光感受器的纤毛旁区，在维持纤毛旁结构和光感受器内外节之间分子的运输方面发挥着重要作用。尽管一些基因显然与该综合征有关，但其他基因仍存在争议。此外，一些 USH 基因的表达已在其他组织中检测到，这可能解释了它们在其他轻度合并症中的参与。本文综述了 Usher 综合征的遗传学及 USH 基因的突变谱。目的是确定与疾病相关的可能突变，并提供最新的基因型-表型相关性。
