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Pediatr Nephrol
2016 Dec 01;3112:2289-2297. doi: 10.1007/s00467-016-3443-0.
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Loss of function of NaPiIIa causes nephrocalcinosis and possibly kidney insufficiency.
Dinour D
,
Davidovits M
,
Ganon L
,
Ruminska J
,
Forster IC
,
Hernando N
,
Eyal E
,
Holtzman EJ
,
Wagner CA
.
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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.
Abecasis,
An integrated map of genetic variation from 1,092 human genomes.
2012, Pubmed
Abecasis,
An integrated map of genetic variation from 1,092 human genomes.
2012,
Pubmed
Beck,
Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities.
1998,
Pubmed
Dinour,
Maternal and infantile hypercalcemia caused by vitamin-D-hydroxylase mutations and vitamin D intake.
2015,
Pubmed
Edvardsson,
Hereditary causes of kidney stones and chronic kidney disease.
2013,
Pubmed
Fenollar-Ferrer,
Structural fold and binding sites of the human Na⁺-phosphate cotransporter NaPi-II.
2014,
Pubmed
Fenollar-Ferrer,
Identification of the first sodium binding site of the phosphate cotransporter NaPi-IIa (SLC34A1).
2015,
Pubmed
,
Xenbase
Halbritter,
Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis.
2015,
Pubmed
Iwaki,
A missense mutation in the sodium phosphate co-transporter Slc34a1 impairs phosphate homeostasis.
2008,
Pubmed
Kenny,
Sotos syndrome, infantile hypercalcemia, and nephrocalcinosis: a contiguous gene syndrome.
2011,
Pubmed
Lapointe,
NPT2a gene variation in calcium nephrolithiasis with renal phosphate leak.
2006,
Pubmed
,
Xenbase
Levtchenko,
Genetic disorders of renal phosphate transport.
2010,
Pubmed
Magen,
Genetic disorders of renal phosphate transport.
2010,
Pubmed
Magen,
A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome.
2010,
Pubmed
,
Xenbase
Myakala,
Renal-specific and inducible depletion of NaPi-IIc/Slc34a3, the cotransporter mutated in HHRH, does not affect phosphate or calcium homeostasis in mice.
2014,
Pubmed
Oddsson,
Common and rare variants associated with kidney stones and biochemical traits.
2015,
Pubmed
Pfister,
Parathyroid hormone-dependent degradation of type II Na+/Pi cotransporters.
1997,
Pubmed
Prié,
Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter.
2002,
Pubmed
,
Xenbase
Rajagopal,
Exome sequencing identifies a novel homozygous mutation in the phosphate transporter SLC34A1 in hypophosphatemia and nephrocalcinosis.
2014,
Pubmed
Reshkin,
Functional asymmetry of phosphate transport and its regulation in opossum kidney cells: phosphate transport.
1990,
Pubmed
Schlingmann,
Mutations in CYP24A1 and idiopathic infantile hypercalcemia.
2011,
Pubmed
Schlingmann,
Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia.
2016,
Pubmed
,
Xenbase
Virkki,
Functional characterization of two naturally occurring mutations in the human sodium-phosphate cotransporter type IIa.
2003,
Pubmed
,
Xenbase
Wagner,
The SLC34 family of sodium-dependent phosphate transporters.
2014,
Pubmed
