Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4)
Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4)
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DOI：
10.1093/hmg/9.11.1709
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发表时间：
2000-07-01
影响因子：
3.5
通讯作者：
Sheffield, VC
中科院分区：
文献类型：
--
作者：
Scott, DA;Wang, R;Sheffield, VC
PDS基因编码一种跨膜蛋白，称为pendrin，其功能是碘和氯的转运蛋白。该基因的突变导致Pendred综合征和染色体7 q31上DFNB 4位点的常染色体隐性非综合征性听力损失。对20名来自美国中西部的非综合征性听力损失和前庭水管扩张的个体进行筛查，发现3人（15%）具有PDS突变。为了确定Pendred综合征个体中的PDS突变是否与非综合征性听力损失个体中的PDS突变在功能上不同，我们比较了三种常见的Pendred综合征等位基因变体。（L236 P、T416 P和E384 G），其中三种PDS突变仅在非综合征性听力损失个体中报告（V480 D、V653 A和1490 L/G497 S）。与Pendred综合征相关的突变完全丧失了pendrin诱导的氯离子和碘离子转运，而DFNB 4患者特有的等位基因能够转运碘离子和氯离子，尽管水平远低于野生型pendrin。我们假设阴离子转运的这种残留水平足以消除或推迟DFNB 4患者甲状腺肿的发作。我们提出了一个pendrin在甲状腺中的功能模型，其中pendrin运输碘穿过甲状腺细胞的顶端膜进入胶体空间。
The PDS gene encodes a transmembrane protein, known as pendrin, which functions as a transporter of iodide and chloride. Mutations in this gene are responsible for Pendred syndrome and autosomal recessive non-syndromic hearing loss at the DFNB4 locus on chromosome 7q31. A screen of 20 individuals from the midwestern USA with non-syndromic hearing loss and dilated vestibular aqueducts identified th ree people (15%) with PDS mutations, To determine whether PDS mutations in individuals with Pendred syndrome differ functionally from PDS mutations in individuals with non-syndromic hearing loss, we compared three common Pendred syndrome allele Variants (L236P, T416P and E384G), with three PDS mutations reported only in individuals with non-syndromic hearing loss (V480D, V653A and 1490L/G497S). The mutations associated with Pendred syndrome have complete loss of pendrin-induced chloride and iodide transport, while alleles unique to people with DFNB4 are able to transport both iodide and chloride, albeit at a much lower level than wild-type pendrin, We hypothesize that this residual level of anion transport is sufficient to eliminate or postpone the onset of goiter in individuals with DFNB4, We propose a model for pendrin function in the thyroid in which pendrin transports iodide across the apical membrane of the thyrocyte into the colloid space.