title: NHERF1 mutations and responsiveness of renal parathyroid hormone.
abstract: Impaired renal phosphate reabsorption, as measured by dividing the tubular maximal reabsorption of phosphate by the glomerular filtration rate (TmP/GFR), increases the risks of nephrolithiasis and bone demineralization. Data from animal models suggest that sodium-hydrogen exchanger regulatory factor 1 (NHERF1) controls renal phosphate transport. We sequenced the NHERF1 gene in 158 patients, 94 of whom had either nephrolithiasis or bone demineralization. We identified three distinct mutations in seven patients with a low TmP/GFR value. No patients with normal TmP/GFR values had mutations. The mutants expressed in cultured renal cells increased the generation of cyclic AMP (cAMP) by parathyroid hormone (PTH) and inhibited phosphate transport. These NHERF1 mutations suggest a previously unrecognized cause of renal phosphate loss in humans.
authors.affiliation: INSERM Unité 845, Université Paris Descartes, Faculté de Médecine, Paris, France.
authors.forename: Zoubida
authors.initials: Z
authors.lastname: Karim
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Gérard
authors.forename: Naziha
authors.initials: N
authors.lastname: Bakouh
authors.forename: Rohia
authors.initials: R
authors.lastname: Alili
authors.forename: Christine
authors.initials: C
authors.lastname: Leroy
authors.forename: Laurent
authors.initials: L
authors.lastname: Beck
authors.forename: Caroline
authors.initials: C
authors.lastname: Silve
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Planelles
authors.forename: Pablo
authors.initials: P
authors.lastname: Urena-Torres
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Gérard
authors.initials: G
authors.lastname: Friedlander
authors.forename: Dominique
authors.initials: D
authors.lastname: Prié
mesh_terms: D000328:Adult; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D018488:Bone Demineralization, Pathologic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis / Q000652:urine; D004252:DNA Mutational Analysis; D005260:Female; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D053565:Hypercalciuria / Q000235:genetics; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D007669:Kidney Calculi / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D053040:Nephrolithiasis / Q000235:genetics* / Q000378:metabolism; D009893:Opossums; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism*; D010710:Phosphates / Q000097:blood / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics*; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics*
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D000242:Cyclic AMP