Abstract
Hereditary 1, 25-dihydroxyvitamin D-resistant rickets (HVDRR), a rare recessive disease, is caused by mutation in the VDR gene encoding the vitamin D receptor leading to the resistance to vitamin D. We described a female toddler with initial presentation of leg tenderness and clinical features of HVDRR including severe rickets, hypocalcemia and hypophosphatemia without alopecia. Genetic analysis revealed novel compound heterozygous mutations of p.M4I and p.H229Q in patient’s VDR gene. In cis p.M4I with FOKI-F eliminated both translation start sites of the VDR protein. The p.H229Q VDR exhibited significantly reduced VDR transactivation activity with intact dimerization with RXR. Our report expanded the mutation spectrum of HVDRR, and provided the first case of a benign variant p.M4I plus a common p.M1T polymorphism leading to a pathogenic allele.
Highlights
Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR, OMIM 277440), known as vitamin D-dependent rickets type II, is a rare autosomal recessive form of vitamin D resistance due to loss of functional vitamin D receptor (VDR)[1]
We described a HVDRR patient without alopecia and identified two novel mutations in the VDR gene, one that alters the VDR mRNA translation initiation site and one that affects vitamin D binding activity
At the age of 5, when her serum iPTH elevated to 715.71 pg/ml, intravenous calcium infusion was given after the course of inpatient hospitalization with the implantation of intravenous catheter
Summary
Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR, OMIM 277440), known as vitamin D-dependent rickets type II, is a rare autosomal recessive form of vitamin D resistance due to loss of functional vitamin D receptor (VDR)[1]. The VDR is expressed in most tissues of the body, including intestine, kidney, bone, and keratinocyte of hair follicles [2, 3]. With the recruitment of co-activators and co-repressors, ligand-activated VDR-RXR complex regulate the expression of multiple target genes in tissue expressing VDR[3]. In HVDRR, the VDR is defective due to mutations in VDR gene, leading to accumulation of high levels of 1,25 (OH)2D3 concentration. Vitamin D-dependent rickets type I which is caused by PLOS ONE | DOI:10.1371/journal.pone.0138152. Vitamin D-dependent rickets type I which is caused by PLOS ONE | DOI:10.1371/journal.pone.0138152 September 30, 2015
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