Glorieux F H, Arabian A, Delvin E E
McGill University, Montréal, Québec, Canada.
J Clin Endocrinol Metab. 1995 Jul;80(7):2255-8. doi: 10.1210/jcem.80.7.7608289.
Pseudo-Vitamin D Deficiency Rickets (PDDR), an heritable defect in renal 25-hydroxyvitamin D 1 alpha-hydroxylase activity, leads to insufficient synthesis of 1 alpha, 25-dihydroxyvitamin D (calcitriol) and the early onset of severe rickets which can only be offset by replacement therapy with calcitriol. The nature of the underlying mutation remains unknown. Hydroxylation of 25-hydroxyvitamin D in the 1 alpha-position is not restricted to the renal tubular cells. We have previously shown that human decidual cells do produce calcitriol and that the enzyme activity was regulated by feedback mechanisms. We now demonstrate that cells isolated from the decidua of PDDR patients lack that function making them likely targets for the mutation. This suggests that the decidual and renal enzymes (or a controller of their activity) are encoded by the same gene. Thus the PDDR placenta represents a source of mutant cells for further investigation of the PDDR molecular defect.
假性维生素D缺乏性佝偻病（PDDR）是一种遗传性的肾脏25-羟维生素D 1α-羟化酶活性缺陷疾病，会导致1α,25-二羟维生素D（骨化三醇）合成不足，进而引发严重佝偻病的早期发作，而这只能通过骨化三醇替代疗法来抵消。潜在突变的性质仍然未知。25-羟维生素D在1α位的羟化并不局限于肾小管细胞。我们之前已经表明，人蜕膜细胞确实能产生骨化三醇，且该酶活性受反馈机制调节。我们现在证明，从PDDR患者蜕膜中分离出的细胞缺乏该功能，这使得它们可能是突变的靶点。这表明蜕膜和肾脏中的酶（或其活性的调控因子）由同一基因编码。因此，PDDR胎盘是用于进一步研究PDDR分子缺陷的突变细胞来源。
