{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T17:13:48Z","timestamp":1718644428916},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Genetic disorders of calcium metabolism arise in a familial or sporadic setting. The calcium-sensing receptor (CASR) plays a key role in maintaining calcium homeostasis and study of the<jats:italic>CASR<\/jats:italic>gene can be clinically useful in determining etiology and appropriate therapeutic approaches. We report two cases of novel<jats:italic>CASR<\/jats:italic>gene mutations that illustrate the varying clinical presentations and discuss these in terms of the current understanding of CASR function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>A 16-year-old patient had mild hypercalcemia associated with low-normal urinary calcium excretion and normal-to-high parathyroid hormone (PTH) levels. Because of negative family history, familial hypocalciuric hypercalcemia was originally excluded. The second patient was a 54-year-old man with symptomatic hypocalcemia, hyperphosphatemia, low PTH, and mild hypercalciuria. Familial investigation revealed the same phenotype in the patient's sister. The coding region of the<jats:italic>CASR<\/jats:italic>gene was sequenced in both probands and their available first-degree relatives.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The first patient had a novel heterozygous inactivating<jats:italic>CASR<\/jats:italic>mutation in exon 4, which predicted a p.A423K change; genetic analysis was negative in the parents. The second patient had a novel heterozygous activating<jats:italic>CASR<\/jats:italic>mutation in exon 6, which predicted a p.E556K change; the affected sister of the proband was also positive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We reported two novel heterozygous mutations of the<jats:italic>CASR<\/jats:italic>gene, an inactivating mutation in exon 4 and the first activating mutation reported to date in exon 6. 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