Familial hypocalciuric hypercalcemia: new mutation in the CASR gene converting valine 697 to methionine

Abstract

Familial hypocalciuric hypercalcemia is an uncommon cause of hypercalcemia that arises from mutations in the calcium-sensing receptor gene. Inactivation of this receptor leads to a decreased receptor sensitivity to calcium, determining that higher concentrations of calcium are needed to inhibit the release of parathormone in the parathyroid glands. Patients usually are asymptomatic. Diagnosis is usually made casually after a routine blood analysis. The syndrome is characterized by mild or moderate hypercalcemia, hypocalciuria, and normal or slightly increased levels of parathormone. The degree of hypercalcemia depends on the type of mutation. The accurate diagnosis is important since it is a benign disorder that does not require medical or surgical treatment. We report a 9-year-old female with persistent hypercalcemia in several routine blood analyses, who was diagnosed with familial hypocalciuric hypercalcemia after genetic studies were performed. A new mutation determining a nucleotide change c.2089G>A in the calcium-sensing receptor gene (exon 7) was detected. This mutation was also found in the patient's mother and brother.

Novel mutations associated with inherited human calcium-sensing receptor disorders: A clinical genetic study

“…In concordance with other studies, we found both inactivating (p.Cys677Tyr, p.Val697Met, p.Phe789del, p.Ile816Val and p.Ile816Thr) and activating (p.Phe788Cys, p.Ser820Phe and p.Gly830Ser) mutations in the transmembrane domain (19,20).…”