ORPHA: 244305; DO: 0080078;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q25.1 | Nephrolithiasis/osteoporosis, hypophosphatemic, 2 | 612287 | Autosomal dominant | 3 | SLC9A3R1 | 604990 |
A number sign (#) is used with this entry because hypophosphatemic nephrolithiasis/osteoporosis-2 (NPHLOP2) is caused by heterozygous mutation in the SLC9A3R1 gene (604990) on chromosome 17q25.
See also NPHLOP1 (612286), caused by mutation in the SLC34A1 gene (182309).
Karim et al. (2008) reported 4 unrelated probands with hypophosphatemia and decreased renal phosphate resorption. Three of the patients had calcium nephrolithiasis, and 1 had a spinal deformity and decreased bone mineral density (BMD). All had significantly decreased tubular maximum for phosphate resorption per glomerular filtration rate (TmP/GFR) values compared to normal, indicating impaired proximal renal tubular phosphate absorption. None of the patients had proximal-tubule dysfunction other than the low TmP/GFR value; they did not have glycosuria, and serum bicarbonate concentrations and blood pH values were normal. Other biochemical findings included increased urinary cAMP excretion and increased serum 1,25-dihydroxyvitamin D (calcitriol).
Karim et al. (2008) demonstrated autosomal dominant inheritance of hypophosphatemic nephrolithiasis/osteoporosis-2.
In 4 of 92 unrelated patients with calcium-containing renal stones (50 patients), bone demineralization (30), or both (12), Karim et al. (2008) identified heterozygous mutations in the SLC9A3R1 gene (604990.0001-604990.0003). In vitro studies indicated that the mutations had no effect on basal phosphate uptake but potentiated parathyroid hormone (PTH; 168450)-induced AMP generation and the inhibition of phosphate transport. The results demonstrated that mutations in the SLC9A3R1 gene can cause renal phosphate loss that may increase the risk of renal stone formation or bone demineralization.
Karim, Z., Gerard, B., Bakouh, N., Alili, R., Leroy, C., Beck, L., Silve, C., Planelles, F., Urena-Torres, P., Grandchamp, B., Friedlander, G., Prie, D. NHERF1 mutations and responsiveness of renal parathyroid hormone. New Eng. J. Med. 359: 1128-1135, 2008. [PubMed: 18784102] [Full Text: https://doi.org/10.1056/NEJMoa0802836]