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A Loss-of-Function Mutation in NaPi-IIa and Renal Fanconi's Syndrome
Ist Teil von
The New England journal of medicine, 2010-03, Vol.362 (12), p.1102-1109
Ort / Verlag
Waltham, MA: Massachusetts Medical Society
Erscheinungsjahr
2010
Quelle
MEDLINE
Beschreibungen/Notizen
Two siblings from a consanguineous family who had autosomal recessive renal Fanconi's syndrome and hypophosphatemic rickets were found to have a homozygous in-frame duplication of 21 bp in
SLC34A1,
the gene that encodes the renal sodium–phosphate cotransporter NaPi-IIa. This mutation results in complete loss of function of the mutant NaPi-IIa, since the transporters fail to reach the plasma membrane. These findings show that disruption of human NaPi-IIa profoundly impairs overall renal phosphate reabsorption and proximal-tubule function.
Two siblings who had renal Fanconi's syndrome and rickets were found to have a mutation in SLC34A1, the gene that encodes the renal sodium̵1;phosphate cotransporter NaPi-IIa. These findings show that disruption of human NaPi-IIa profoundly impairs overall renal phosphate reabsorption and proximal-tubule function.
Renal phosphate handling occurs predominantly in the proximal tubule, where 70 to 80% of filtered phosphate is recovered.
1
Two principal phosphate transporters, NaPi-IIa and NaPi-IIc, have been identified on the apical membrane of the mammalian proximal tubule.
2
,
3
Although extensively studied in murine models, in which NaPi-IIa serves as the predominant mediator of renal phosphate reabsorption,
4
,
5
the importance of NaPi-IIa in regulating renal phosphate handling in humans remains controversial. To date, mutations in the
SLC34A1
gene, which encodes NaPi-IIa, have not been found to cause any known human form of hereditary hypophosphatemic rickets or proximal tubulopathy. Sequence variants in . . .