Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome:: low prevalence and phenotypic variability
Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome:: low prevalence and phenotypic variability
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DOI：
10.1111/j.1399-0004.2004.00352.x
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发表时间：
2004-12-01
影响因子：
3.5
通讯作者：
Millán, JM
中科院分区：
文献类型：
--
作者：
Aller, E;Jaijo, T;Millán, JM
Usher综合征III型是一种常染色体隐性遗传病，临床特征为视网膜色素变性（RP）、前庭功能障碍的可变存在和进行性听力损失的关联，是听力损害的进展，是区分该形式与Usher综合征I型和Usher综合征II型的关键参数。亚瑟小子综合征III型临床亚型是西班牙亚瑟小子综合征最罕见的亚型，仅占西班牙亚瑟小子综合征全部病例的6%。导致Usher综合征III型的基因被命名为clarin-1，它被认为与毛细胞和光感受器细胞突触有关。在这里，我们报告在我们的一系列Usher综合征西班牙患者中筛选clarin-1基因突变。Clarin-1仅在两个家族中被发现与该疾病有关：第一个是先前报道的Y63X突变的家族纯合子，第二个是C40G突变的纯合子。这占1.7%的鄂榭综合症西班牙家庭。值得注意的是，由于听力损失的进展，C40G家族在临床上与Usher综合征III型相适应，而Y63X家族由于听力损害的深度和稳定性，可诊断为Usher综合征I型。因此，我们认为听力损失的进展并不是区分Usher综合征III型与Usher综合征I型和Usher综合征II型的决定性关键参数。
Usher syndrome type III is an autosomal recessive disorder clinically characterized by the association of retinitis pigmentosa (RP), variable presence of vestibular dysfunction and progressive hearing loss, being the progression of the hearing impairment the critical parameter classically used to distinguish this form from Usher syndrome type I and Usher syndrome type II. Usher syndrome type III clinical subtype is the rarest form of Usher syndrome in Spain, accounting only for 6% of all Usher syndrome Spanish cases. The gene responsible for Usher syndrome type III is named clarin-1 and it is thought to be involved in hair cell and photoreceptor cell synapses. Here, we report a screening for mutations in clarin-1 gene among our series of Usher syndrome Spanish patients. Clarin-1 has been found to be responsible for the disease in only two families: the first one is a previously reported family homozygous for Y63X mutation and the second one, described here, is homozygous for C40G. This accounts for 1.7% of Usher syndrome Spanish families. It is noticeable that, whereas C40G family is clinically compatible with Usher syndrome type III due to the progression of the hearing loss, Y63X family could be diagnosed as Usher syndrome type I because the hearing impairment is profound and stable. Thus, we consider that the progression of hearing loss is not the definitive key parameter to distinguish Usher syndrome type III from Usher syndrome type I and Usher syndrome type II.