No evidence for point mutations of the calcium-sensing receptor in familial idiopathic hypercalciuria

Background. Idiopathic hypercalciuria (IH) is frequently associated with ne phrolithiasis. As 40% of patients have a positive familial history of IH, a n 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 pro spective study. Forty-two family members underwent 24-h urine calcium measu rement. Twenty-five of them with 24-h hypercalciuria also underwent extensi ve metabolic evaluation. Blood samples were collected in one or two affecte d family members in each family and exons 2-7 of the CaR gene were sequence d. Results. In the seven families, at least one parent and more than half of t he 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 hy percalciuria, and one had renal phosphorous leak. No mutation of the CaR ge ne was detected in these seven families. Two previously reported polymorphi sms were detected, each of them in five families: A986S and C-to-T change a t -60 in intron 5. Conclusion. In these seven families, IH is not related to the CaR gene muta tion. Although we cannot exclude that point mutations can be found in other families, familial IH does not seem to be generally associated with CaR mu tation.