Nephrol Dial Transplant (2001) 16: 2317-2322
© 2001 European Renal Association-European Dialysis and Transplant Association
No evidence for point mutations of the calcium-sensing receptor in familial idiopathic hypercalciuria
1 Service de Néphrologie A, Hôpital Tenon, Paris, 2 Laboratoire de génétique moléculaire, Hôpital Tenon, Paris, 3 Laboratoire d'explorations fonctionnelles, Hôpital Tenon, Paris, 4 Laboratoire d'explorations fonctionnelles, Hôpital Broussais, Paris, 5 Service d'Urologie, Hôpital Tenon, Paris, 6 Laboratoire de génétique moléculaire, Hôpital Broussais, Paris and 7 Service de Néphrologie B, Hôpital Tenon, Paris, France
Background. Idiopathic hypercalciuria (IH) is frequently associated with nephrolithiasis. As 40% of patients have a positive familial history of IH, an autosomal dominant mode of inheritance has been suggested. Numerous genes have been studied in this regard but none have been found to be linked to IH. Mutation of the calcium-sensing receptor (CaR) has never been studied. Therefore, we conducted a study to detect such mutations.
Methods. Seven families with IH and nephrolithiasis were recruited in a prospective study. Forty-two family members underwent 24-h urine calcium measurement. Twenty-five of them with 24-h hypercalciuria also underwent extensive metabolic evaluation. Blood samples were collected in one or two affected family members in each family and exons 2–7 of the CaR gene were sequenced.
Results. In the seven families, at least one parent and more than half of the children had hypercalciuria (21/30), consistent with autosomal dominant inheritance. Among the nine affected family members whose CaR gene has been studied, all nine had absorptive hypercalciuria, three also had fasting hypercalciuria, and one had renal phosphorous leak. No mutation of the CaR gene was detected in these seven families. Two previously reported polymorphisms were detected, each of them in five families: A986S and C-to-T change at -60 in intron 5.
Conclusion. In these seven families, IH is not related to the CaR gene mutation. Although we cannot exclude that point mutations can be found in other families, familial IH does not seem to be generally associated with CaR mutation.
Keywords: calcium-sensing receptor; DNA mutational analysis; idiopathic hypercalciuria; kidney calculi
Correspondence and offprint requests to: Prof. E. Rondeau, Service de Néphrologie A, Hôpital Tenon, 4 rue de la Chine, F-75020 Paris, France. Email: loeric.rondeau{at}tnn.ap\|[hyphen]\|hop\|[hyphen]\|paris.fr
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Bevilacqua, L. J. Dominguez, V. Righini, V. Valdes, R. Toscano, O. Sangaletti, T. Vago, G. Baldi, M. Barrella, and G. Bianchi-Porro Increased Gastrin and Calcitonin Secretion after Oral Calcium or Peptones Administration in Patients with Hypercalciuria: A Clue to an Alteration in Calcium-Sensing Receptor Activity J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1489 - 1494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. W. Moe and O. Bonny Genetic Hypercalciuria J. Am. Soc. Nephrol., March 1, 2005; 16(3): 729 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Houillier and M. Paillard Calcium-sensing receptor and renal cation handling Nephrol. Dial. Transplant., December 1, 2003; 18(12): 2467 - 2470. [Full Text] [PDF]
|
|
|
|
|
|
G. Vezzoli, A. Tanini, L. Ferrucci, L. Soldati, C. Bianchin, F. Franceschelli, C. Malentacchi, B. Porfirio, D. Adamo, A. Terranegra, et al. Influence of Calcium-Sensing Receptor Gene on Urinary Calcium Excretion in Stone-Forming Patients J. Am. Soc. Nephrol., October 1, 2002; 13(10): 2517 - 2523. [Abstract] [Full Text] [PDF]
|
|