A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome

Daniella Magen, Liron Berger, Michael J. Coady, Anat Ilivitzki, Daniela Militianu, Martin Tieder, Sara Selig, Jean Yves Lapointe, Israel Zelikovic, Karl Skorecki

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171 Scopus citations

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.

Original languageEnglish
Pages (from-to)1102-1109
Number of pages8
JournalNew England Journal of Medicine
Volume362
Issue number12
DOIs
StatePublished - 25 Mar 2010
Externally publishedYes

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