A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome.
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Magen D, Berger L, Coady MJ, Ilivitzki A, Militianu D, Tieder M, Selig S, Lapointe JY, Zelikovic I, Skorecki K
A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome.
N Engl J Med. 2010 Mar 25;362(12):1102-9. doi: 10.1056/NEJMoa0905647.
- PubMed ID
- 20335586 [ View in PubMed]
- Abstract
We describe two siblings from a consanguineous family with autosomal recessive Fanconi's syndrome and hypophosphatemic rickets. Genetic analysis revealed a homozygous in-frame duplication of 21 bp in SLC34A1, which encodes the renal sodium-inorganic phosphate cotransporter NaPi-IIa, as the causative mutation. Functional studies in Xenopus laevis oocytes and in opossum kidney cells indicated complete loss of function of the mutant NaPi-IIa, resulting from failure of the transporter to reach the plasma membrane. These findings show that disruption of the human NaPi-IIa profoundly impairs overall renal phosphate reabsorption and proximal-tubule function and provide evidence of the critical role of NaPi-IIa in human renal phosphate handling.