Chromosomal localization of the human renal sodium phosphate transporter to chromosome 5: implications for X-linked hypophosphatemia

Abstract

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.

Fig. 1.

Somatic cell hybrid panel was digested with BamHI restriction enzyme and probed with a 2-kb genomic fragment of the phosphate gene labeled with ³²P deoxycytidine triphosphate. A hybridization band was seen corresponding to chromosome 5.

Fig. 2.

PCR amplification of somatic cell hybrids using subset I. Amplification is seen in lanes corresponding to the human control but not to the hamster. The numbers at the top of the panel are cell line designations. The bands amplified in A correspond to chromosome 5. Cell lines 423 and 811 do not contain chromosome 5. Part B confirms the findings in A, with cell line 324 showing no amplification because it does not contain chromosome 5.

Fig. 3.

FISH. Hybridization is seen on chromosome 5q 13.