A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection.
In this report, we describe a female patient with VDDR2A caused by an early stop codon (R30X) in the VDR gene that resulted in a severely truncated VDR protein.
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.
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.
Vitamin D receptors from patients with resistance to 1,25-dihydroxyvitamin D3: point mutations confer reduced transactivation in response to ligand and impaired interaction with the retinoid X receptor heterodimeric partner.
A new point mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor in a kindred with hereditary 1,25-dihydroxyvitamin D-resistant rickets.
<b>Context:</b> Vitamin D-dependent rickets type 2A (VDDR2A) is a rare autosomal recessive disorder and is caused by mutations in the vitamin D receptor gene (<i>VDR</i>), leading to end-organ resistance to 1,25(OH)<sup>2</sup>D<sup>3</sup>.
The introduction of another variable, the ER genotype, in the analysis of VDR genetic determination of BMD, may represent a useful model in the identification of patients at risk of developing a multigenic disorder like osteoporosis.
The risk of osteoporosis in the VDR-rs2228570 polymorphism T-allele carriers was significantly higher than that in CC (CT/TT versus CC) individuals (adjusted odds ratio [OR] [95% confidence interval (CI)] = 1.76 [1.33-2.22]).
Association analyses and multivariate two-step regression model of social and molecular parameters, demonstrated that in comparison to the VDR, ESR, CTR polymorphisms, physical activities and healthy diet, associated with outdoor work are the best favourable prognostic factors for osteoporosis.
In conclusion, these data, along with the absence of relationships between VDR gene polymorphisms and peak bone mass that we recently reported, suggest that the determination of VDR genotypes is probably not a useful clinical test for the risk assessment of osteoporosis.
Recent developments in the molecular epidemiology of osteoporosis have shown the interest, but also the limitations, of specific molecular markers, such as the vitamin D receptor gene polymorphisms Bsm 1 and Fok 1, to explain bone mineral density differences across the population.
A series of common polymorphisms in the vitamin D receptor gene were recently reported to be associated with bone density and risk of osteoporosis (Morrison et al., Nature (Lond.), 367: 284-287, 1994).