Mutation of the CYP2R1 Vitamin D 25-Hydroxylase in a Saudi Arabian Family with Severe Vitamin D Deficiency

被引:58
|
作者
Al Mutair, Angham N. [1 ,2 ]
Nasrat, Ghada H.
Russell, David W. [3 ]
机构
[1] King Saud Bin Abdulaziz Univ Hlth Sci, Coll Med, Dept Pediat, King Abdulaziz Med City Riyadh,Div Endocrinol, Riyadh 11155, Saudi Arabia
[2] King Abdullah Int Med Res Ctr, Riyadh 11155, Saudi Arabia
[3] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA
来源
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2012年 / 97卷 / 10期
关键词
RICKETS; GENE;
D O I
10.1210/jc.2012-1340
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: 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 1 alpha,25-dihydroxyvitamin D receptor, CYP27B1, encoding the vitamin D 1 alpha-hydroxylase, and CYP2R1, encoding a microsomal vitamin D 25-hydroxylase. Results: 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. Conclusion: We conclude that CYP2R1 is a major vitamin D 25-hydroxylase that plays a fundamental role in activation of this essential vitamin. (J Clin Endocrinol Metab 97: E2022-E2025, 2012)
引用
收藏
页码:E2022 / E2025
页数:4
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