Loss-of-Function ENPP1 Mutations Cause Both Generalized Arterial Calcification of Infancy and Autosomal-Recessive Hypophosphatemic Rickets
Loss-of-Function ENPP1 Mutations Cause Both Generalized Arterial Calcification of Infancy and Autosomal-Recessive Hypophosphatemic Rickets
复制标题
DOI：
10.1016/j.ajhg.2010.01.006
复制
发表时间：
2010-02-12
影响因子：
9.8
通讯作者：
Strom, Tim M.
中科院分区：
文献类型：
--
作者：
Lorenz-Depiereux, Bettina;Schnabel, Dirk;Strom, Tim M.
对影响磷酸盐稳态的罕见遗传性疾病的分析导致鉴定出对磷酸盐稳态的肾脏调节至关重要的几种蛋白质;例如，成纤维细胞生长因子23（FGF 23），其抑制肾脏磷酸盐重吸收和1，25-二羟基维生素D合成。在这里，我们报告推测的功能缺失突变ENPP1基因（外核苷酸焦磷酸酶/磷酸二酯酶）的四个家庭成员受低磷血症性佝偻病。我们提供的证据表明，ENPP 1是第四个基因，除了PHEX，FGF23，和DMP1，如果突变，导致低磷酸盐血症佝偻病的FGF23水平升高。令人惊讶的是，ENPP 1功能丧失突变先前已在婴儿期的全身性动脉钙化中被描述，这表明了一种迄今尚不明确的平衡动脉钙化与骨矿化的机制。
The analysis of rare genetic disorders affecting phosphate homeostasis led to the identification of several proteins that are essential for the renal regulation of phosphate homeostasis; for example, fibroblast growth factor 23 (FGF23), which inhibits renal phosphate reabsorption and 1,25-dihydroxy-vitamin D synthesis. Here, we report presumable loss-of-function mutations in the ENPP1 gene (ectonucleotide pyrophosphatase/phosphodiesterase) in members of four families affected with hypophosphatemic rickets. We provide evidence for the conclusion that ENPP1 is the fourth gene-in addition to PHEX, FGF23, and DMP1-that, if mutated, causes hypophosphatemic rickets resulting from elevated FGF23 levels. Surprisingly, ENPP1 loss-of-function Mutations have previously been described in generalized arterial calcification of infancy, suggesting an as yet elusive mechanism that balances arterial calcification with bone mineralization.