A loss-of-function mutation in NaPi-IIa and renal Fanconi''s syndrome.
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.
PubMed ID: 20335586
Article link: N Engl J Med.
Grant support: MOP-10580 Canadian Institutes of Health Research