USH3A transcripts encode clarin-1, a four- transmembrane-domain protein with a possible role in sensory synapses
USH3A transcripts encode clarin-1, a four- transmembrane-domain protein with a possible role in sensory synapses
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DOI：
10.1038/sj.ejhg.5200831
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发表时间：
2002-06-01
影响因子：
5.2
通讯作者：
Lancet, D
中科院分区：
文献类型：
--
作者：
Adato, A;Vreugde, S;Lancet, D
Usher综合征3型（USH3）是一种常染色体隐性遗传病，其特征是与语后进行性听力丧失、视网膜色素变性导致的进行性视力丧失和前庭功能障碍的可变存在相关。由于先前定义的转录本并不能解释所有的USH3病例，我们进行了进一步的分析，发现在更长的人类和小鼠USH3A转录本中存在额外的外显子，以及三种新的USH3A突变。Ush3a转录本在耳蜗毛细胞和螺旋神经节细胞中表达。全长USH3A转录本编码clarin-1，这是一种四跨膜结构域蛋白，它定义了一个新的脊椎动物特异性家族。与stargazin（一种小脑突触四跨膜结构域蛋白）的有限序列同源性表明clarin-1在毛细胞和光感受器细胞突触中的作用，以及不同Usher综合征的共同病理生理途径。
Usher syndrome type 3 (USH3) is an autosomal recessive disorder characterised by the association of post-lingual progressive hearing loss, progressive visual loss due to retinitis pigmentosa and variable presence of vestibular dysfunction. Because the previously defined transcripts do not account for all USH3 cases, we performed further analysis and revealed the presence of additional exons embedded in longer human and mouse USH3A transcripts and three novel USH3A mutations. Expression of Ush3a transcripts was localised by whole mount in situ hybridisation to cochlear hair cells and spiral ganglion cells. The full length USH3A transcript encodes clarin-1, a four-transmembrane-domain protein, which defines a novel vertebrate-specific family of three paralogues. Limited sequence homology to stargazin, a cerebellar synapse four-transmembrane-domain protein, suggests a role for clarin-1 in hair cell and photoreceptor cell synapses, as well as a common pathophysiological pathway for different Usher syndromes.