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04.07.2016 | Original Article

Loss of function of NaPiIIa causes nephrocalcinosis and possibly kidney insufficiency

verfasst von: Dganit Dinour, Miriam Davidovits, Liat Ganon, Justyna Ruminska, Ian C. Forster, Nati Hernando, Eran Eyal, Eli J. Holtzman, Carsten A. Wagner

Erschienen in: Pediatric Nephrology | Ausgabe 12/2016

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Abstract

Background

Inherited metabolic disorders associated with nephrocalcinosis are rare conditions. The aim of this study was to identify the genetic cause of an Israeli-Arab boy from a consanguineous family with severe nephrocalcinosis and kidney insufficiency.

Methods

Clinical and biochemical data of the proband and family members were obtained from both previous and recent medical charts. Genomic DNA was isolated from peripheral blood cells. The coding sequence and splice sites of candidate genes (CYP24A1, CYP27B1, FGF23, KLOTHO, SLC34A3 and SLC34A1) were sequenced directly. Functional studies were performed in Xenopus laevis oocytes and in transfected opossum kidney (OK) cells.

Results

Our patient was identified as having nephrocalcinosis in utero, and at the age of 16.5 years, he had kidney insufficiency but no bone disease. Genetic analysis revealed a novel homozygous missense mutation, Arg215Gln, in SLC34A1, which encodes the renal sodium phosphate cotransporter NaPiIIa. Functional studies of the Arg215Gln mutant revealed reduced transport activity in Xenopus laevis oocytes and increased intracellular cytoplasmic accumulation in OK cells.

Conclusions

Our findings show that dysfunction of the human NaPiIIa causes severe renal calcification that may eventually lead to reduced kidney function, rather than complications of phosphate loss.

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Titel: Loss of function of NaPiIIa causes nephrocalcinosis and possibly kidney insufficiency
verfasst von: Dganit Dinour
Miriam Davidovits
Liat Ganon
Justyna Ruminska
Ian C. Forster
Nati Hernando
Eran Eyal
Eli J. Holtzman
Carsten A. Wagner
Publikationsdatum: 04.07.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology / Ausgabe 12/2016
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-016-3443-0

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Loss of function of NaPiIIa causes nephrocalcinosis and possibly kidney insufficiency

Abstract

Background

Methods

Results

Conclusions

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Springer Medizin

Abstract

Background

Methods

Results

Conclusions

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