scholarly journals Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness.

1997 ◽  
Vol 99 (2) ◽  
pp. 297-304 ◽  
Author(s):  
P J Malloy ◽  
T R Eccleshall ◽  
C Gross ◽  
L Van Maldergem ◽  
R Bouillon ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Novel Mutation ◽  
Vitamin D Resistant Rickets ◽  
Resistant Rickets

A Case of Hereditary Vitamin D-Resistant Rickets (HVDRR) without Alopecia: A Novel Mutation

2011 ◽  
pp. P2-116-P2-116
Author(s):  
Karen Eileen Huang ◽  
Peter J Malloy ◽  
Debra Jeandron ◽  
David Feldman ◽  
Pisit Pitukcheewanont
Keyword(s):  
Vitamin D ◽  
Novel Mutation ◽  
Vitamin D Resistant Rickets ◽  
Resistant Rickets

scholarly journals Hereditary 1,25-Dihydroxyvitamin D Resistant Rickets due to a Mutation Causing Multiple Defects in Vitamin D Receptor Function

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5106-5114 ◽  
Author(s):  
Peter J. Malloy ◽  
Rong Xu ◽  
Lihong Peng ◽  
Sara Peleg ◽  
Abdullah Al-Ashwal ◽  
...  
Keyword(s):  
Vitamin D ◽  
Ligand Binding ◽  
Vitamin D Receptor ◽  
Novel Mutation ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Retinoid X Receptor ◽  
Vdr Gene ◽  
Dihydroxyvitamin D3 ◽  
Resistant Rickets

Abstract Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disease caused by mutations in the vitamin D receptor (VDR). We studied a young Saudi Arabian girl who exhibited the typical clinical features of HVDRR, but without alopecia. Analysis of her VDR gene revealed a homozygous T to C mutation in exon 7 that changed isoleucine to threonine at amino acid 268 (I268T). From crystallographic studies of the VDR ligand-binding domain, I268 directly interacts with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and is involved in the hydrophobic stabilization of helix H12. We recreated the I268T mutation and analyzed its effects on VDR function. In ligand binding assays, the I268T mutant VDR exhibited an approximately 5- to 10-fold lower affinity for [3H]1,25(OH)2D3 compared with the wild-type (WT) VDR. The I268T mutant required approximately a 65-fold higher concentration of 1,25(OH)2D3 to be equipotent in gene transactivation. Both retinoid X receptor heterodimerization and coactivator binding were reduced in the I268T mutant. Analogs of 1,25(OH)2D3 have been proposed as potential therapeutics for patients with HVDRR. Interestingly, in protease sensitivity assays, treatment with the potent vitamin D analog, 20-epi-1,25(OH)2D3, stabilized I268T mutant proteolytic fragments better than 1,25(OH)2D3. Moreover, 20-epi-1,25(OH)2D3 restored transactivation of the I268T mutant to levels exhibited by WT VDR treated with 1,25(OH)2D3. In conclusion, we describe a novel mutation, I268T, in the VDR ligand-binding domain that alters ligand binding, retinoid X receptor heterodimerization, and coactivator binding. These combined defects in VDR function cause resistance to 1,25(OH)2D3 action and result in the syndrome of HVDRR.

A homozygous mutation in the DNA binding domain of human vitamin D receptor causes vitamin D resistant rickets

Bone ◽  
2012 ◽  
Vol 50 ◽  
pp. S43
Author(s):  
B.C. van der Eerden⁎ ◽  
J.C. van der Heyden ◽  
J.P. van Hamburg ◽  
M. Schreuders-Koedam ◽  
P.S. Asmawidjaja ◽  
...  
Keyword(s):  
Vitamin D ◽  
Dna Binding ◽  
Vitamin D Receptor ◽  
Binding Domain ◽  
Homozygous Mutation ◽  
Dna Binding Domain ◽  
Vitamin D Resistant Rickets ◽  
Resistant Rickets

Hereditary vitamin D-resistant rickets in Lebanese patients: the p.R391S and p.H397P variants have different phenotypes

2017 ◽  
Vol 30 (4) ◽  
Author(s):  
Rabih Andary ◽  
Abdul-Karim El-Hage-Sleiman ◽  
Theresa Farhat ◽  
Sami Sanjad ◽  
Georges Nemer
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Sanger Sequencing ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Normal Phenotype ◽  
Vitamin D Resistant Rickets ◽  
Exon 9 ◽  
Homozygous Mutations ◽  
Resistant Rickets

Abstract:Background:Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder caused by mutations in the vitamin D receptor (Methods:We examined four patients with HVDRR from three unrelated Lebanese families. All parents were consanguineous with normal phenotype. We used Sanger sequencing to identify mutations in the coding exons ofResults:Two homozygous mutations (p.R391S and p.H397P), both in exon 9 of theConclusions:This is the first report of

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