CYP24A1基因失功能突变导致高钙血症及尿石症
作者：Dganit Dinour, Pazit Beckerman, Liat Ganon, Karen Tordjman, et al. 来源：Journal of Urology 日期：2013-03-12
导读
Loss-of-function mutations of CYP24A1, the vitamin D 24- hydroxylase gene, cause long-standing hypercalciuric nephrolithiasis and nephrocalcinosis
Abstract
Purpose
Hypercalciuria is the most common cause of kidney stone disease. Genetic factors play an important role in almost half of those cases. Recently, loss-of-function mutations of CYP24A1, the gene encoding Vitamin D-24-hydroxylase, were identified in idiopathic infantile hypercalcemia. We describe the clinical and molecular basis of adults with a severe long standing kidney stone disease caused by CYP24A1 mutations.
Materials and Methods
Three subjects from two Israeli families with nephrolithiasis and nephrocalcinosis were clinically characterized. Genomic DNA was isolated from peripheral blood, and sequencing of CYP24A1 was performed.
Results
All subjects presented with severe kidney stone disease, the cause of which was not unveiled for decades despite extensive evaluation. They all had hypercalciuria, nephrocalcinosis and intermittent hypercalcemia, and the oldest subject developed chronic kidney insufficiency. All patients had a typical pattern of tests, including normal-high serum calcium, low PTH levels, high vitamin D 25(OH)D3 and 1,25(OH)2 D3 and low 24,25(OH)2 D3. Three CYP24A1 loss-of-function mutations were identified: a homozygous deletion (delE143) in the consanguinous family 1 and compound heterozygous mutations, L409S and the novel W268-stop, in family 2.
Conclusions
Loss-of-function mutations of CYP24A1 gene, encoding for 1,25-dihydroxyvitamin D3 24-hydroxylase, cause severe hypercalciuric nephrolithiasis and nephrocalcinosis. It may present in adults and may lead to chronic renal insufficiency. Our results support a recessive mode of inheritance. CYP24A1 mutations should be considered in the differential diagnosis of hypercalciuric nephrolithiasis, especially in a time when many of the adult population are prescribed supplemental oral vitamin D.
http://www.jurology.com/article/S0022-5347(13)03464-2/abstract
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