Two hereditary defects related to vitamin D metabolism map to the same region of human chromosome 12q13-14.

We have localized the locus for the vitamin D receptor (VDR) responsible for hypocalcemic vitamin D-resistant rickets (HVDRR), close to the pseudovitamin D-deficient rickets (PDDR) locus, another disorder related to impaired vitamin D metabolism. PDDR (formerly vitamin D dependency type I, VDD1) was recently mapped to human chromosome 12q14 by linkage analysis. Here we report on the assignment of VDR to 12q13-14 by in situ hybridization and by linkage analysis. Linkage analysis between VDR, PDDR, and several RFLP markers show close linkage, with no recombination (theta = 0) between VDR and PDDR (Z = 1.94), a COL2A1 haplotype (Z = 4.03), ELA1 (Z = 0.98), and D12S15 (Z = 4.17). The analysis of extended haplotypes in one of the PDDR families provides evidence for recombination between VDR and PDDR and localizes VDR together with COL2A1 proximal to PDDR. Complete allelic association detected between VDR and COL2A1 loci on PDDR chromosomes and lower association between VDR and PDDR suggests a VDR location very close to COL2A1 and one more distant to PDDR. We propose the following order of loci: (VDR, COL2A1), (PDDR, ELA1, D12S15), D12S4, (D12S14, D12S17), D12S6. Thus, two clearly distinct loci involved in the control of vitamin D activity map close to each other in the region 12q13-14.