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    
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.
Nikta Forghani; Catherine Lum; Sowmya Krishnan; Jining Wang; Darrel M Wilson; Piers R Blackett; Peter J Malloy; David Feldman
Related Documents :
20375209 - Clinical review 2: genetic determinants of bone density and fracture risk--state of the...
10091149 - Genetic and acquired predisposing factors and treatment of osteoporosis in thalassaemia...
10523819 - Association of the serotonin transporter promoter regulatory region polymorphism and ob...
18036039 - Association of vitamin d receptor gene taq i polymorphism with recurrent urolithiasis i...
18195729 - Glycogen synthase kinase-3beta gene is associated with antidepressant treatment respons...
11704489 - Seeking genetic causes of "osteoporosis:" insights of the utah paradigm of skeletal phy...
15539439 - No association of estrogen receptor alpha and cytochrome p450c17alpha polymorphisms wit...
17584019 - Genetic polymorphism of the flavin-containing monooxygenase 3 (fmo3) associated with tr...
9688889 - "physiological genomics": mutant screens in zebrafish.
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Alopecia / genetics*
Biological Markers / metabolism
Child, Preschool
Codon, Nonsense*
DNA Mutational Analysis
Drug Resistance
Enzyme Induction / drug effects
Fibroblasts / drug effects,  metabolism,  pathology
Gene Expression / drug effects
Receptors, Calcitriol / genetics*,  metabolism
Rickets / genetics*
Skin / drug effects,  metabolism,  pathology
Steroid Hydroxylases / biosynthesis
Vitamin D / analogs & derivatives,  pharmacology,  therapeutic use
Grant Support
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 D 24-hydroxylase

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

Previous Document:  McCune-Albright syndrome (MAS): early and extensive bone fibrous dysplasia involvement and "mistaken...
Next Document:  Secondary hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss in the subacute...