The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD)
The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD)
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DOI：
10.1086/421527
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发表时间：
2004-06-01
影响因子：
9.8
通讯作者：
Itakura, M
中科院分区：
文献类型：
--
作者：
Tsutsumi, S;Kamata, N;Itakura, M
摘要颚骨干发育不良是一种罕见的骨骼症候群，其特徴为骨骼脆弱、管状骨硬化及颚骨的牙骨质病变。通过对一个日本GDD大家族的连锁分析，我们先前将GDD基因定位于染色体11p14.3-15.1。在重组作图确定的关键区域，我们确定了一个新的基因（GDD 1），编码一个913个氨基酸的蛋白质含有8个假定的跨膜结构域。在两个GDD家族（原始日本家族和一个新的非洲裔美国人家族）中发现了GDD 1的两个错义突变（C356 R和C356 G），这两个错义突变都发生在第356位氨基酸的半胱氨酸残基上，这在人类、小鼠、斑马鱼、果蝇和蚊子中是进化上保守的。细胞定位于内质网表明GDD 1在调节细胞内钙稳态中的作用。
Gnathodiaphyseal dysplasia (GDD) is a rare skeletal syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of the jawbone. By linkage analysis of a large Japanese family with GDD, we previously mapped the GDD locus to chromosome 11p14.3-15.1. In the critical region determined by recombination mapping, we identified a novel gene (GDD1) that encodes a 913-amino-acid protein containing eight putative transmembrane-spanning domains. Two missense mutations (C356R and C356G) of GDD1 were identified in the two families with GDD (the original Japanese family and a new African American family), and both missense mutations occur at the cysteine residue at amino acid 356, which is evolutionarily conserved among human, mouse, zebrafish, fruit fly, and mosquito. Cellular localization to the endoplasmic reticulum suggests a role for GDD1 in the regulation of intracellular calcium homeostasis.