Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II
Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II
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DOI：
10.1086/381685
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发表时间：
2004-02-01
影响因子：
9.8
通讯作者：
Kimberling, WJ
中科院分区：
文献类型：
--
作者：
Weston, MD;Luijendijk, MWJ;Kimberling, WJ
Usher综合征II型（USH 2）是一种遗传异质性常染色体隐性遗传疾病，至少有三种遗传亚型（USH 2A、USH 2B和USH 2C），表型分类为先天性听力损失和进行性视网膜色素变性。VLGR 1（MASS 1）基因在5q14.3-q21.1 USH 2C基因座被认为是一个可能的候选人的基础上，其蛋白质基序结构和表达序列标签表示从耳蜗和视网膜消减文库。变性高效液相色谱和聚合酶链反应产物的直接测序扩增10个遗传独立的USH 2C和156例USH 2患者确定了四个亚型特异性VLGR 1突变（Q2301 X，I2906 FS，M2931 FS和T6244 X）从三个家庭USH 2C，以及两个散发病例。所有VLGR 1突变患者均为女性，这与随机预期存在显著偏差。VLGR 1蛋白的配体尚不清楚，但基于其潜在的细胞外和细胞内蛋白质-蛋白质相互作用结构域及其广泛的mRNA表达谱，VLGR 1可能服务于不同的细胞和信号传导过程。VLGR 1突变先前已在人类和小鼠中鉴定，并且与两个物种中的反射性癫痫发作表型相关。鉴定额外的VLGR 1突变，以测试是否存在表型/基因型相关性，类似于其他Usher综合征疾病基因，是必要的。
Usher syndrome type II (USH2) is a genetically heterogeneous autosomal recessive disorder with at least three genetic subtypes (USH2A, USH2B, and USH2C) and is classified phenotypically as congenital hearing loss and progressive retinitis pigmentosa. The VLGR1 (MASS1) gene in the 5q14.3-q21.1 USH2C locus was considered a likely candidate on the basis of its protein motif structure and expressed-sequence-tag representation from both cochlear and retinal subtracted libraries. Denaturing high-performance liquid chromatography and direct sequencing of polymerase-chain-reaction products amplified from 10 genetically independent patients with USH2C and 156 other patients with USH2 identified four isoform-specific VLGR1 mutations (Q2301X, I2906FS, M2931FS, and T6244X) from three families with USH2C, as well as two sporadic cases. All patients with VLGR1 mutations are female, a significant deviation from random expectations. The ligand(s) for the VLGR1 protein is unknown, but on the basis of its potential extracellular and intracellular protein-protein interaction domains and its wide mRNA expression profile, it is probable that VLGR1 serves diverse cellular and signaling processes. VLGR1 mutations have been previously identified in both humans and mice and are associated with a reflex-seizure phenotype in both species. The identification of additional VLGR1 mutations to test whether a phenotype/genotype correlation exists, akin to that shown for other Usher syndrome disease genes, is warranted.