Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.
Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.
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DOI：
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发表时间：
1996-02
影响因子：
9.8
通讯作者：
J. Hästbacka;A. Superti-Furga;W. Wilcox;D. Rimoin;D. Cohn;E. Lander
中科院分区：
文献类型：
--
作者：
J. Hästbacka;A. Superti-Furga;W. Wilcox;D. Rimoin;D. Cohn;E. Lander
II型关节发育（AO II）是一种新生儿致死性软骨发育不良，其临床和组织学特征类似于另一种软骨发育不良，严重程度要轻得多的异型发育不良（DTD）。这种相似性表明在相同的生化途径和可能相同的基因中有一个涉及病变的共同发病机制。DTD是由最近发现的硫酸盐转运基因（DTDST）突变引起的。在这里，我们报道AOII患者也有DTDST突变，这导致体外患者间充质细胞对无机硫酸盐的摄取缺陷和大分子硫酸化不足。再加上我们最近观察到的第三种甚至更严重的软骨发育不良，即IB型软骨发育不全，也是由DTDST突变引起的，这些结果表明，由单个硫酸盐转运体基因的病变引起的三种严重程度不断增加的软骨发育不良的表型系列。表型的严重程度似乎与突变对DTDST蛋白残留活性的预测影响相关。
Atelosteogenesis type II (AO II) is a neonatally lethal chondrodysplasia whose clinical and histological characteristics resemble those of another chondrodysplasia, the much less severe diastrophic dysplasia (DTD). The similarity suggests a shared pathogenesis involving lesions in the same biochemical pathway and perhaps the same gene. DTD is caused by mutations in the recently identified diastrophic dysplasia sulfate-transporter gene (DTDST). Here, we report that AOII patients also have DTDST mutations, which lead to defective uptake of inorganic sulfate and insufficient sulfation of macromolecules by patient mesenchymal cells in vitro. Together with our recent observation that a third even more severe chondrodysplasia, achondrogenesis type IB, is also caused by mutations in DTDST, these results demonstrate a phenotypic series of three chondrodysplasias of increasing severity caused by lesions in a single sulfate-transporter gene. The severity of the phenotype appears to be correlated with the predicted effect of the mutations on the residual activity of the DTDST protein.