Dasgupta, Debayan ORCID: 0000-0002-1064-0541, Wee, Mark J., Reyes, Monica, Li, Yuwen, Simm, Peter J., Sharma, Amita, Schlingmann, Karl-Peter, Janner, Marco, Biggin, Andrew ORCID: 0000-0002-3443-9359, Lazier, Joanna, Gessner, Michaela, Chrysis, Dionisios, Tuchman, Shamir, Baluarte, H. Jorge, Levine, Michael A., Tiosano, Dov, Insogna, Karl ORCID: 0000-0001-6973-5679, Hanley, David A., Carpenter, Thomas O., Ichikawa, Shoji, Hoppe, Bernd, Konrad, Martin, Saevendahl, Lars, Munns, Craig F., Lee, Hang, Jueppner, Harald and Bergwitz, Clemens (2014). Mutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis. J. Am. Soc. Nephrol., 25 (10). S. 2366 - 2376. WASHINGTON: AMER SOC NEPHROLOGY. ISSN 1533-3450

Full text not available from this repository.

Abstract

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 from those 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 (P<0.001). Renal calcifications were also more frequent in het carriers (16%; P=0.003 compared with the general population) and were more likely to occur in comp/hom and het individuals with decreased serum phosphate (odds ratio [OR], 0.75, 95% confidence interval [95% CI], 0.59 to 0.96; P=0.02), decreased tubular reabsorption of phosphate (OR, 0.41; 95% CI, 0.23 to 0.72; P=0.002), and increased serum 1,25(OH)(2) 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dasgupta, DebayanUNSPECIFIEDorcid.org/0000-0002-1064-0541UNSPECIFIED
Wee, Mark J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reyes, MonicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, YuwenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simm, Peter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sharma, AmitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlingmann, Karl-PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janner, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Biggin, AndrewUNSPECIFIEDorcid.org/0000-0002-3443-9359UNSPECIFIED
Lazier, JoannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gessner, MichaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chrysis, DionisiosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tuchman, ShamirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baluarte, H. JorgeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levine, Michael A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tiosano, DovUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Insogna, KarlUNSPECIFIEDorcid.org/0000-0001-6973-5679UNSPECIFIED
Hanley, David A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carpenter, Thomas O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ichikawa, ShojiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoppe, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konrad, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saevendahl, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munns, Craig F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, HangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jueppner, HaraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergwitz, ClemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-427632
DOI: 10.1681/ASN.2013101085
Journal or Publication Title: J. Am. Soc. Nephrol.
Volume: 25
Number: 10
Page Range: S. 2366 - 2376
Date: 2014
Publisher: AMER SOC NEPHROLOGY
Place of Publication: WASHINGTON
ISSN: 1533-3450
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HEREDITARY HYPOPHOSPHATEMIC RICKETS; VITAMIN-D; IDIOPATHIC HYPERCALCIURIA; PHOSPHATE HOMEOSTASIS; INTRONIC DELETIONS; GENE; BONE; NEPHROLITHIASIS; REABSORPTION; METABOLISMMultiple languages
Urology & NephrologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42763

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item