Hypophosphatemic vitamin D-resistant rickets, an X-linked dominant disorder, is the most common form of
vitamin D-resistant rickets in humans (McKusick number 307800). Biochemically, these patients exhibit
hypophosphatemia due to a defect in the renal tubular reabsorption of
phosphate. The human
cDNA encoding for the renal
phosphate transporter has been recently cloned using the expression system in the Xenopus laevis oocytes. Because
hypophosphatemic vitamin D-resistant rickets has an X-linked mode of transmission, we hypothesized that the gene encoding the renal
phosphate transporter might map to the X chromosome. In this report, we determined the chromosomal localization of the human renal
phosphate transporter using three independent methods. First,
DNA from somatic cell hybrid panels was examined by Southern blotting for the
phosphate transporter. Second, the polymerase chain reaction was used to amplify
DNA from somatic cell hybrids. Third, fluorescent in situ hybridization was used to sublocalize the renal
phosphate transporter. All three methods localized the renal
phosphate transporter to chromosome 5q13. Our results indicate that either derangement of a gene other than the
phosphate transporter gene that is encoded on chromosome 5 is responsible for
X-linked hypophosphatemic rickets or, alternatively, a gene encoded on the X chromosome has an epistatic effect on the expression of the renal
phosphate transporter on chromosome 5.