Document Detail


Two new unrelated cases of hereditary 1,25-dihydroxyvitamin D-resistant rickets with alopecia resulting from the same novel nonsense mutation in the vitamin D receptor gene.
MedLine Citation:
PMID:  21073129     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) an important regulator of bone homeostasis, mediates its actions by binding to the vitamin D receptor (VDR), a nuclear transcription factor. Mutations in the VDR cause the rare genetic disease hereditary vitamin D resistant rickets (HVDRR). In this study, we examined two unrelated young female patients who exhibited severe early onset rickets, hypocalcemia, and hypophosphatemia. Both patients had partial alopecia but with different unusual patterns of scant hair. Sequencing of the VDR gene showed that both patients harbored the same unique nonsense mutation that resulted in a premature stop codon (R50X). Skin fibroblasts from patient #1 were devoid of VDR protein and 1,25(OH)2D3 treatment of these cells failed to induce CYP24A1 gene expression, a marker of 1,25(OH)2D3 action. In conclusion, we identified a novel nonsense mutation in the VDR gene in two patients with HVDRR and alopecia. The mutation truncates the VDR protein and causes 1,25(OH)2D3 resistance.
Authors:
Nikta Forghani; Catherine Lum; Sowmya Krishnan; Jining Wang; Darrel M Wilson; Piers R Blackett; Peter J Malloy; David Feldman
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of pediatric endocrinology & metabolism : JPEM     Volume:  23     ISSN:  0334-018X     ISO Abbreviation:  J. Pediatr. Endocrinol. Metab.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-11-15     Completed Date:  2010-11-30     Revised Date:  2014-01-13    
Medline Journal Info:
Nlm Unique ID:  9508900     Medline TA:  J Pediatr Endocrinol Metab     Country:  England    
Other Details:
Languages:  eng     Pagination:  843-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alopecia / genetics*
Biological Markers / metabolism
Child, Preschool
Codon, Nonsense*
DNA Mutational Analysis
Drug Resistance
Enzyme Induction / drug effects
Female
Fibroblasts / drug effects,  metabolism,  pathology
Gene Expression / drug effects
Humans
Receptors, Calcitriol / genetics*,  metabolism
Rickets / genetics*
Skin / drug effects,  metabolism,  pathology
Steroid Hydroxylases / biosynthesis
Vitamin D / analogs & derivatives,  pharmacology,  therapeutic use
Grant Support
ID/Acronym/Agency:
DK042482/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Codon, Nonsense; 0/Receptors, Calcitriol; 1406-16-2/Vitamin D; 66772-14-3/1,25-dihydroxyvitamin D; EC 1.14.-/Steroid Hydroxylases; EC 1.14.13.126/vitamin D 24-hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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