Finding Sheds Light on Renal Fanconi's Syndrome in Siblings
Homozygous duplication in gene encoding NaPi-IIa implicated in disease in adult brother, sister
WEDNESDAY, March 24 (HealthDay News) -- A homozygous duplication in the SLC34A1 gene, which encodes the renal sodium-inorganic phosphate cotransporter NaPi-IIa, was found to be the cause of autosomal recessive renal Fanconi's syndrome and hypophosphatemic rickets in a sibling pair, according to research published in the March 25 issue of the New England Journal of Medicine.
Daniella Magen, M.D., of the Rambam Health Care Campus in Haifa, Israel, and colleagues analyzed data from an adult brother and sister, from a consanguineous Israeli Arab family, who had been described in a study two decades earlier. In childhood, they had hypophosphatemic rickets and proximal tubulopathy.
The researchers found that both individuals had a homozygous in-frame duplication of 21 bp in SLC34A1, leading to duplication of seven amino acids in the NaPi-IIa protein. The duplication was missing in 100 matched controls. Further investigation using Xenopus laevis oocytes and opossum kidney cells found complete loss of function of mutant NaPi-IIa, due to failure of the transporter to reach the plasma membrane.
Their finding of the association between the duplication in SLC34A1 and the disease in the siblings "provides a human model for the loss of function of NaPi-IIa, constitutes evidence for the inclusion of NaPi-IIa in the list of proteins involved in human hypophosphatemic rickets and proximal tubulopathy, and validates the pivotal role of the human NaPi-IIa cotransporter in renal phosphate handling and in the maintenance of whole-body phosphate homeostasis," the authors conclude.