Department of Pediatrics, Endocrinology Division, King Abdulaziz Medical City-Riyadh, College of Medicine, King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh 11155, Kingdom of Saudi Arabia.
J Clin Endocrinol Metab. 2012 Oct;97(10):E2022-5. doi: 10.1210/jc.2012-1340. Epub 2012 Aug 1.
Inherited forms of vitamin D deficiency are rare causes of rickets and to date have been traced to mutations in three genes, VDR, encoding the 1α,25-dihydroxyvitamin D receptor, CYP27B1, encoding the vitamin D 1α-hydroxylase, and CYP2R1, encoding a microsomal vitamin D 25-hydroxylase.
Multiple mutations have been identified in VDR and CYP27B1 in patients with rickets, and thus, the roles of these two genes in vitamin D metabolism are unassailable. The case is less clear for CYP2R1, in which only a single mutation, L99P in exon 2 of the gene, has been identified in Nigerian families, and because multiple enzymes with vitamin D 25-hydroxylase activity have been identified. Here we report molecular genetic studies on two siblings from a Saudi family who presented with classic symptoms of vitamin D deficiency. The affected offspring inherited two different CYP2R1 mutations (367+1, G→A; 768, iT), which are predicted to specify null alleles.
We conclude that CYP2R1 is a major vitamin D 25-hydroxylase that plays a fundamental role in activation of this essential vitamin.
遗传性维生素 D 缺乏症是佝偻病的罕见病因，迄今为止，已追踪到三种基因突变，分别是编码 1α,25-二羟维生素 D 受体的 VDR 基因、编码维生素 D 1α-羟化酶的 CYP27B1 基因和编码微粒体维生素 D 25-羟化酶的 CYP2R1 基因。
在佝偻病患者中已经发现 VDR 和 CYP27B1 存在多种突变，因此这两种基因在维生素 D 代谢中的作用是无可置疑的。对于 CYP2R1 情况则不太明确，仅在尼日利亚家族中发现该基因第 2 外显子的 L99P 单一突变，而且有多种具有维生素 D 25-羟化酶活性的酶被鉴定。在此，我们报道了一对沙特家族的同胞兄妹的分子遗传学研究，他们表现出典型的维生素 D 缺乏症状。受影响的后代遗传了两种不同的 CYP2R1 突变（367+1，G→A；768，iT），这两种突变预计指定无效等位基因。
我们得出结论，CYP2R1 是一种主要的维生素 D 25-羟化酶，在这种必需维生素的激活中起着重要作用。
