CHROMOSOMAL LOCALIZATION OF THE HUMAN RENAL SODIUM-PHOSPHATE TRANSPORTER TO CHROMOSOME-5 - IMPLICATIONS FOR X-LINKED HYPOPHOSPHATEMIA

Hypophosphatemic vitamin D-resistant rickets, an X-linked dominant dis order, is the most common form of vitamin D-resistant rickets in human s (McKusick number 307800). Biochemically, these patients exhibit hypo phosphatemia due to a defect in the renal tubular reabsorption of phos phate. The human cDNA encoding for the renal phosphate transporter has been recently cloned using the expression system in the Xenopus laevi s 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 thi s report, we determined the chromosomal localization of the human rena l phosphate transporter using three independent methods. First, DNA fr om somatic cell hybrid panels was examined by Southern blotting for th e phosphate transporter. Second, the polymerase chain reaction was use d 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 chrom osome 5q13. Our results indicate that either derangement of a gene oth er than the phosphate transporter gene that is encoded on chromosome 5 is responsible for X-linked hypophosphatemic rickets or, alternativel y, a gene encoded on the X chromosome has an epistatic effect on the e xpression of the renal phosphate transporter on chromosome 5.