{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:01:43Z","timestamp":1789182103302,"version":"build-2803163510"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Familial hypocalciuric hypercalcemia (FHH) type 1 is caused by mutations in the gene encoding the calcium-sensing receptor (<jats:italic>CASR<\/jats:italic>). Recently, mutations affecting codon 15 in the gene <jats:italic>AP2S1<\/jats:italic> have been shown to cause FHH type 3 in up to 26% of <jats:italic>CASR<\/jats:italic>-negative FHH patients. Similarly, mutations in the gene G<jats:italic>NA11<\/jats:italic> have been shown to cause FHH type 2. We hypothesized that mutations in <jats:italic>AP2S1<\/jats:italic> and <jats:italic>GNA11<\/jats:italic> are causative in Danish patients with suspected FHH and that these mutations are not found in patients with primary hyperparathyroidism (PHPT), which is the main differential diagnostic disorder.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>Cross-sectional study.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We identified patients with unexplained hyperparathyroid hypercalcemia and a control group of verified PHPT patients through review of 421 patients tested for <jats:italic>CASR<\/jats:italic> mutations in the period 2006\u20132014. DNA sequencing of all amino acid coding exons including intron\u2013exon boundaries in <jats:italic>AP2S1<\/jats:italic> and <jats:italic>GNA11<\/jats:italic> was performed.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>In 33 <jats:italic>CASR<\/jats:italic>-negative patients with suspected FHH, we found two (~6%) with a mutation in <jats:italic>AP2S1<\/jats:italic> (p.Arg15Leu and p.Arg15His). Family screening confirmed the genotype\u2013phenotype correlations. We did not identify any pathogenic mutations in <jats:italic>GNA11<\/jats:italic>. No pathogenic mutations were found in the PHPT control group.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We suggest that the best diagnostic approach to hyperparathyroid hypercalcemic patients suspected to have FHH is to screen the <jats:italic>CASR<\/jats:italic> and <jats:italic>AP2S1<\/jats:italic> codon 15 for mutations. If the results are negative and there is still suspicion of an inherited condition (i.e. family history), then <jats:italic>GNA11<\/jats:italic> should be examined.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-16-0842","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T13:16:27Z","timestamp":1479302187000},"page":"177-185","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":26,"title":["AP2S1 and GNA11 mutations \u2013 not a common cause of familial hypocalciuric hypercalcemia"],"prefix":"10.1093","volume":"176","author":[{"given":"Silje","family":"Hovden","sequence":"first","affiliation":[{"name":"1Departments of Clinical Biochemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Rejnmark","sequence":"additional","affiliation":[{"name":"2Endocrinology and Internal MedicineAarhus University Hospital, Aarhus N, 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