Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis

Debayan Dasgupta, Mark J. Wee, Monica Reyes, Yuwen Li, Peter J. Simm, Amita Sharma, Karl Peter Schlingmann, Marco Janner, Andrew Biggin, Joanna Lazier, Michaela Gessner, Dionisios Chrysis, Shamir Tuchman, H. Jorge Baluarte, Michael A. Levine, Dov Tiosano, Karl Insogna, David A. Hanley, Thomas O. Carpenter, Shoji IchikawaBernd Hoppe, Martin Konrad, Lars Sävendahl, Craig F. Munns, Hang Lee, Harald Jüppner, Clemens Bergwitz

Research output: Contribution to journalArticlepeer-review


Compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na+)-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate wasting resulting in hypophosphatemia, correspondingly elevated 1,25(OH)2 vitamin D levels, hypercalciuria, and rickets/osteomalacia. Similar, albeit less severe, biochemical changes are observed in heterozygous (het) carriers and indistinguishable fromthose changes encountered in idiopathic hypercalciuria (IH). Here, we report a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and two cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p.G457S]; c.367delC) were identified. Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46%compared with 6%observed in healthy family members carrying only the wild-type SLC34A3 allele (P=0.005) or 5.64% in the general population (P2 vitamin D(OR, 1.22;95%CI, 1.05 to 1.41; P=0.008). Additional studies are needed to determine whether these biochemical parameters are independent of genotype and can guide therapy to prevent nephrocalcinosis, nephrolithiasis, and potentially, CKD.

Original languageEnglish (US)
Pages (from-to)2366-2375
Number of pages10
JournalJournal of the American Society of Nephrology
Issue number10
StatePublished - Oct 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis'. Together they form a unique fingerprint.

Cite this