1/24. oral manifestations of Schimmelpenning syndrome: case report and review of literature.Schimmelpenning syndrome (SS) is characterised by specific skin manifestations, skeletal defects, and central nervous system abnormalities. Here, the SS is briefly reviewed, and the oral and dental manifestations are described in a patient whose medical findings were previously published and included severe hypophosphatemic rickets. Significant oral and dental features included papillomatous lesions of the gingiva, hemihyperplasia (hemihypertrophy) of the tongue, bone cysts, aplasia of teeth, enlarged pulp chambers, hypoplastic or absent enamel, and an odontodysplasia-like permanent tooth.- - - - - - - - - - ranking = 1keywords = rickets (Clic here for more details about this article) |
2/24. Atrichia caused by mutations in the vitamin d receptor gene is a phenocopy of generalized atrichia caused by mutations in the hairless gene.Generalized atrichia with papules is a rare disorder characterized by loss of hair shortly after birth and development of cutaneous cysts. Mutations in the hairless gene (HR) cause this phenotype in both mouse and human. Here we present a case of atrichia with papules in a patient with a normal HAIRLESS gene but with mutations in both alleles of the vitamin d RECEPTOR. The patient exhibited vitamin d resistant rickets, which was confirmed by an absent response of her fibroblasts to 1,25-dihydroxyvitamin D3 in vitro. Similar to individuals with HAIRLESS mutations, her skin showed an absence of normal hair follicles and the presence of follicular remnants and cysts. The cyst epithelium contained keratin-15- and keratin-17-positive cells suggesting derivation from the hair follicle bulge and the presence of epithelial stem cells. Although hair loss has been reported in association with hereditary vitamin d resistant rickets, we now characterize this alopecia as clinically and pathologically indistinguishable from generalized atrichia with papules, which was previously thought to be caused only by mutations in HAIRLESS. These findings suggest that VDR and HR, which are both zinc finger proteins, may be in the same genetic pathway that controls postnatal cycling of the hair follicle.- - - - - - - - - - ranking = 2.1095151304343keywords = rickets, vitamin (Clic here for more details about this article) |
3/24. A novel mutation in helix 12 of the vitamin d receptor impairs coactivator interaction and causes hereditary 1,25-dihydroxyvitamin D-resistant rickets without alopecia.Hereditary vitamin d-resistant rickets (HVDRR) is a genetic disorder most often caused by mutations in the vitamin d receptor (VDR). The patient in this study exhibited the typical clinical features of HVDRR with early onset rickets, hypocalcemia, secondary hyperparathyroidism, and elevated serum concentrations of alkaline phosphatase and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D(3)]. The patient did not have alopecia. Assays of the VDR showed a normal high affinity low capacity binding site for [(3)H]1,25-(OH)(2)D(3) in extracts from the patient's fibroblasts. However, the cells were resistant to 1,25-dihydroxyvitamin D action as demonstrated by the failure of the patient's cultured fibroblasts to induce the 24-hydroxylase gene when treated with either high doses of 1,25-(OH)(2)D(3) or vitamin d analogs. A novel point mutation was identified in helix H12 in the ligand-binding domain of the VDR that changed a highly conserved glutamic acid at amino acid 420 to lysine (E420K). The patient was homozygous for the mutation. The E420K mutant receptor recreated by site-directed mutagenesis exhibited many normal properties including ligand binding, heterodimerization with the retinoid X receptor, and binding to vitamin d response elements. However, the mutant VDR was unable to elicit 1,25-(OH)(2)D(3)-dependent transactivation. Subsequent studies demonstrated that the mutant VDR had a marked impairment in binding steroid receptor coactivator 1 (SRC-1) and DRIP205, a subunit of the vitamin d receptor-interacting protein (DRIP) coactivator complex. Taken together, our data indicate that the mutation in helix H12 alters the coactivator binding site preventing coactivator binding and transactivation. In conclusion, we have identified the first case of a naturally occurring mutation in the VDR (E420K) that disrupts coactivator binding to the VDR and causes HVDRR.- - - - - - - - - - ranking = 6.2346752795022keywords = rickets, vitamin (Clic here for more details about this article) |
4/24. Vitamin-D-dependent rickets type 2.Vitamin-D-dependent rickets type 2 results from autosomal recessive mutations of the vitamin d receptor gene. With congenital total body alopecia and onset of rickets during the second half of the first year of life, patients display rapidly progressing rachitic bone changes, hypocalcemia and secondary hyperparathyroidism. This article describes extensive personal experience with about one third of the world's reported cases, their clinical course, the physiological consequences, diagnostic steps, molecular findings and therapeutic approach, as they developed over the course of the last 25 years.- - - - - - - - - - ranking = 6.0156450186335keywords = rickets, vitamin (Clic here for more details about this article) |
5/24. vitamin d-dependent rickets Type II with alopecia: two case reports and review of the literature.vitamin d-dependent rickets Type II is a rare autosomal recessive disorder. It usually presents with rachitic changes not responsive to vitamin d treatment with elevated circulating levels of 1,25-Dihydroxyvitamin D3, thus differentiating it from vitamin d-dependent rickets Type I. alopecia of the scalp or the body is seen in some families with vitamin d-dependent rickets Type II. This is usually associated with more severe resistance to vitamin d. We report two Saudi brothers with this disease, and review the salient features of this disease with emphasis on the associated alopecia.- - - - - - - - - - ranking = 7.0156450186335keywords = rickets, vitamin (Clic here for more details about this article) |
6/24. Clinical and pathologic correlations in genetically distinct forms of atrichia.BACKGROUND: The genetic basis of 2 distinct forms of atrichia with papules has recently been defined at the molecular level. In atrichia with papular lesions (APL; Online Mendelian Inheritance in Man [OMIM] 209500), mutations in the hairless gene on chromosome 8p21 have recently been identified. Atrichia with papules also occurs in the clinical setting of vitamin d-dependent rickets type IIA (VDDR IIA; OMIM 277440), resulting from mutations in the vitamin d receptor gene on chromosome 12q12-q14. Despite the distinct genetic basis for both forms of atrichia, the clinical findings are strikingly similar and exhibit classic pathognomonic features unique to this phenotype. We sought to document the clinical and molecular features of APL and VDDR IIA. OBSERVATIONS: Molecular analysis of the hairless and vitamin d receptor genes was performed on genomic dna from probands and family members from 3 families with APL and 2 with VDDR IIA. We present a clinical and histologic comparison of atrichia in patients with APL and VDDR IIA and highlight the genetically heterogeneous basis of atrichia by identification of pathogenetic mutations. CONCLUSIONS: Increased awareness of these diseases will allow early diagnosis and potential therapeutic intervention for the rickets in VDDR IIA and avoidance of treatment of the atrichia in both APL and VDDR IIA. Their phenotype similarities suggest the possibility of a functional relationship between HR and VDR.- - - - - - - - - - ranking = 2.0469350559004keywords = rickets, vitamin (Clic here for more details about this article) |
7/24. Hereditary 1,25-dihydroxyvitamin D resistant rickets due to a mutation causing multiple defects in vitamin d receptor function.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 D(3) [1,25(OH)(2)D(3)] 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 [(3)H]1,25(OH)(2)D(3) compared with the wild-type (WT) VDR. The I268T mutant required approximately a 65-fold higher concentration of 1,25(OH)(2)D(3) 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)(2)D(3) 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)(2)D(3), stabilized I268T mutant proteolytic fragments better than 1,25(OH)(2)D(3). Moreover, 20-epi-1,25(OH)(2)D(3) restored transactivation of the I268T mutant to levels exhibited by WT VDR treated with 1,25(OH)(2)D(3). 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)(2)D(3) action and result in the syndrome of HVDRR.- - - - - - - - - - ranking = 5.1877402236017keywords = rickets, vitamin (Clic here for more details about this article) |
8/24. A girl with a novel splice site mutation in VDR supports the role of a ligand-independent VDR function on hair cycling.Mutations in vitamin d receptor (VDR) cause hereditary vitamin d resistant rickets (HVDRR). We reported a Thai girl with HVDRR, presenting with an early onset of rickets and partial alopecia. She was a product of a consanguineous couple. Mutation analysis showed that she was homozygous for a novel splice site mutation of the VDR gene, 462 1 G --> C, resulting in incorporation of the whole 254 bp of the intron 4 into its mRNA. The mutated protein is expected to contain no ligand-binding domain. The fact that she did not develop total alopecia despite of no VDR ligand-binding domain supports that VDR function on hair cycling is ligand independent.- - - - - - - - - - ranking = 2.031290037267keywords = rickets, vitamin (Clic here for more details about this article) |
9/24. rickets with alopecia: an inborn error of vitamin d metabolism.rickets with alopecia, an inborn error of vitamin d metabolism, is described in two sisters. The rachitic disorder began during the first year of life and was refractory to 50,000 IU of vitamin D2/day. Surprisingly, both children had marked elevations in serum concentrations of 1,25-(OH)2D. Although the molecular basis for this disorder is not evident to date, intestinal end-organ unresponsiveness to exceedingly high levels of 1,25-(OH)2D was present, in addition to hyporesponsiveness of bone to these high levels of the hormone, since normocalcemia was maintained despite elevated serum levels of PTH. Therapy with oral 1,25-(OH)2D3 failed to reverse the disorder, but oral phosphorus supplements resulted in significant radiographic and clinical improvement.- - - - - - - - - - ranking = 0.093870111800864keywords = vitamin (Clic here for more details about this article) |
10/24. alopecia with rickets: an end organ unresponsiveness to 1,25-dihydroxyvitamin D--a case report.Two siblings of a rare syndrome of vitamin d dependent type II rickets are reported for the first time from india. The clinical and biochemical picture was characterised by florid rickets, alopecia, hypocalcemia and resistance to therapy with high dosages of vitamin D3. Due to lack of facilities for estimation of 1,25(OH)2D, alopecia remains the only clue to the diagnosis of this rare syndrome in association with resistant rickets.- - - - - - - - - - ranking = 7.0938701118009keywords = rickets, vitamin (Clic here for more details about this article) |
| | Next -> |