{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T01:28:23Z","timestamp":1775093303796,"version":"3.50.1"},"reference-count":13,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:00:00Z","timestamp":1567987200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    Familial hypocalciuric hypercalcaemia (FHH) is a genetic disorder of altered calcium homeostasis. Mutations in the\n                    <ns4:italic>CASR<\/ns4:italic>\n                    ,\n                    <ns4:italic>GNA11<\/ns4:italic>\n                    and\n                    <ns4:italic>AP2S1<\/ns4:italic>\n                    genes have been reported to cause FHH. We report a Hong Kong Chinese kindred with FHH type 3 (FHH3) caused by mutations in\n                    <ns4:italic>AP2S1<\/ns4:italic>\n                    . The proband, a 51-year-old woman with hypercalcaemia, was initially diagnosed to have primary hyperparathyroidism but repeated parathyroidectomy failed to normalize her plasma calcium concentrations. Later, FHH was suspected and yet no mutations were identified in the\n                    <ns4:italic>CASR<\/ns4:italic>\n                    gene which causes FHH type 1 (FHH1), the most common form of FHH. Genetic testing of\n                    <ns4:italic>AP2S1<\/ns4:italic>\n                    revealed a heterozygous c.43C&gt;T (p.Arg15Cys) mutation, confirming the diagnosis of FHH3. The elder brother and niece of the proband, who both have hypercalcaemia, were found to harbour the same mutation. To our knowledge, this is the first Chinese kindred of FHH3 reported in the English literature.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.20344.1","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T11:05:06Z","timestamp":1568027106000},"page":"1612","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["A Hong Kong Chinese kindred with familial hypocalciuric hypercalcaemia caused by AP2S1 mutation"],"prefix":"10.12688","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5160-0063","authenticated-orcid":false,"given":"Felix Chi Kin","family":"Wong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wai Sheung","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey Sung Shing","family":"Kwok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa Kam Chi","family":"Tsui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kam Piu","family":"Lau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael Ho Ming","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuet Ping","family":"Yuen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"275-282","DOI":"10.1016\/j.ceca.2003.10.010","article-title":"Diseases associated with the extracellular calcium-sensing receptor.","volume":"35","author":"R Thakker","year":"2004","journal-title":"Cell Calcium."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"1297-1303","DOI":"10.1016\/0092-8674(93)90617-y","article-title":"Mutations in the human Ca2+-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.","volume":"75","author":"M Pollak","year":"1993","journal-title":"Cell."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"2476-2486","DOI":"10.1056\/NEJMoa1300253","article-title":"Mutations affecting G-protein subunit \u03b111 in hypercalcemia and hypocalcemia.","volume":"368","author":"M Nesbit","year":"2013","journal-title":"N Engl J Med."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"93-97","DOI":"10.1038\/ng.2492","article-title":"Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3.","volume":"45","author":"M Nesbit","year":"2013","journal-title":"Nat Genet."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"397-412","DOI":"10.1097\/00005792-198111000-00002","article-title":"The hypocalciuric or benign variant of familial hypercalcemia: clinical and biochemical features in fifteen kindreds.","volume":"60","author":"S Marx","year":"1981","journal-title":"Medicine (Baltimore)."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"511-519","DOI":"10.7326\/0003-4819-102-4-511","article-title":"Familial benign hypercalcemia (hypocalciuric hypercalcemia). Clinical and pathogenetic studies in 21 families.","volume":"102","author":"W Law","year":"1985","journal-title":"Ann Intern Med."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"122-133","DOI":"10.1038\/ncpendmet0388","article-title":"Clinical lessons from the calcium-sensing receptor.","volume":"3","author":"E Brown","year":"2007","journal-title":"Nat Clin Pract Endocrinol Metab."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"1947-1954","DOI":"10.1210\/jc.2009-2152","article-title":"Identification of a second kindred with familial hypocalciuric hypercalcemia type 3 (FHH3) narrows localization to a <3.5 megabase pair region on chromosome 19q13.3.","volume":"95","author":"M Nesbit","year":"2010","journal-title":"J Clin Endocrinol Metab."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"177-185","DOI":"10.1530\/EJE-16-0842","article-title":"AP2S1 and GNA11 mutations - not a common cause of familial hypocalciuric hypercalcemia.","volume":"176","author":"S Hovden","year":"2017","journal-title":"Eur J Endocrinol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"2185-2195","DOI":"10.1210\/jc.2015-3442","article-title":"Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences.","volume":"101","author":"R Vargas-Poussou","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"741-747","DOI":"10.1007\/s12020-017-1241-5","article-title":"Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia.","volume":"55","author":"A Szalat","year":"2017","journal-title":"Endocrine."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"5079-5092","DOI":"10.1093\/hmg\/ddv226","article-title":"Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects.","volume":"24","author":"F Hannan","year":"2015","journal-title":"Hum Mol Genet."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"1396-1398","DOI":"10.1056\/NEJMc1511646","article-title":"Cinacalcet for Symptomatic Hypercalcemia Caused by AP2S1 Mutations","volume":"374","author":"S Howles","year":"2016","journal-title":"N Engl J Med."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/8-1612\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-1612\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-1612\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T13:11:08Z","timestamp":1572613868000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/8-1612\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,9]]},"references-count":13,"URL":"https:\/\/doi.org\/10.12688\/f1000research.20344.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.22357.r55718","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.22357.r54581","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.22357.r54582","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.22357.r54582","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.22357.r55718","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.22357.r54581","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,9]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/8-1612\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.22357.r54581, Caroline Gorvin, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK, 16 Oct 2019, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/8-1612\/v1#referee-response-54581","order":0,"name":"referee-response-54581","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.22357.r54582, Fadil M. Hannan, Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK, 21 Oct 2019, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/8-1612\/v1#referee-response-54582","order":1,"name":"referee-response-54582","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.22357.r55718, Pascal Houillier, Department of Physiology, Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France, 01 Nov 2019, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/8-1612\/v1#referee-response-55718","order":2,"name":"referee-response-55718","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}