{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:09:18Z","timestamp":1791857358934,"version":"4.3.4"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK113039"],"award-info":[{"award-number":["R01DK113039"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1DK046718"],"award-info":[{"award-number":["RO1DK046718"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We report on 2 patients of East African ancestry with the same novel homozygous variant in the parathyroid hormone receptor type 1 (PTH1R). Both patients shared skeletal features, including brachydactyly, extensive metacarpal pseudo-epiphyses, elongated cone-shaped epiphyses, ischiopubic hypoplasia, and deficient sacral ossification, suggestive of Eiken syndrome. Strikingly, both patients exhibited clinically manifest parathyroid hormone (PTH) resistance with hypocalcemia and elevated serum phosphate levels. These laboratory and clinical abnormalities initially suggested pseudohypoparathyroidism, which is typically associated with GNAS abnormalities. In both patients, however, a homozygous novel PTH1R variant was identified (c.710\u00a0T\u2009&amp;gt;\u2009A; p.IIe237Asn, p.I237N) that is located in the second transmembrane helical domain. Previously, others have reported a patient with a nearby PTH1R mutation (D241E) who presented with similar clinical features (eg, delayed bone mineralization as well as clinical PTH resistance). Functional analysis of the effects of both novel PTH1R variants (I237N- and D241E-PTH1R) in HEK293 reporter cells transfected with plasmid DNA encoding the wild-type or mutant PTH1Rs demonstrated increased basal cAMP signaling for both variants, with relative blunting of responses to both PTH and PTH-related peptide (PTHrP) ligands. The clinical presentation of PTH resistance and delayed bone mineralization combined with the functional properties of the mutant PTH1Rs suggest that this form of Eiken syndrome results from alterations in PTH1R-mediated signaling in response to both canonical ligands, PTH and PTHrP.<\/jats:p>","DOI":"10.1093\/jbmr\/zjae148","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T22:33:46Z","timestamp":1726180426000},"page":"1596-1605","source":"Crossref","is-referenced-by-count":8,"title":["Eiken syndrome with parathyroid hormone resistance due to a novel parathyroid hormone receptor type 1 mutation: clinical features and functional analysis"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8335-299X","authenticated-orcid":false,"given":"Alistair D","family":"Calder","sequence":"first","affiliation":[{"name":"Radiology Department, Great Ormond Street Hospital for Children NHS Foundation Trust , London WC1N 3JH,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Allgrove","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Great Ormond Street Hospital for Children NHS Foundation Trust , London WC1N 3JH,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"H\u00f6ppner","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira","family":"Cheung","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Great Ormond Street Hospital for Children NHS Foundation Trust , London WC1N 3JH,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saji","family":"Alexander","sequence":"additional","affiliation":[{"name":"Paediatrics, Chelsea and Westminster Hospital NHS Foundation Trust , London, SW10 9JH,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Garagnani","sequence":"additional","affiliation":[{"name":"Hand Unit and Department of Orthopaedics, Guy\u2019s and St Thomas\u2019s Hospital NHS Foundation Trust , London, SE1 9RT","place":["United Kingdom"]},{"name":"King\u2019s College London , London, WC2R 2LS","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Thakker","sequence":"additional","affiliation":[{"name":"Academic Endocrine Unit , Radcliffe Department of Medicine, , Oxford, OX3 7LE,","place":["United Kingdom"]},{"name":"University of Oxford , Radcliffe Department of Medicine, , Oxford, OX3 7LE,","place":["United Kingdom"]},{"name":"National Institute for Health Research Oxford Biomedical Research Centre , Oxford, OX3 9DU","place":["United Kingdom"]},{"name":"Centre for Endocrinology , William Harvey Research Institute, Barts and the London School of Medicine, , London, EC1M 6BQ,","place":["United Kingdom"]},{"name":"Queen Mary University of London , William Harvey Research Institute, Barts and the London School of Medicine, , London, EC1M 6BQ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"J\u00fcppner","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Gardella","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Holder-Espinasse","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Guy\u2019s Hospital, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust , London, SE1 9RT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"issue":"2","key":"2024103012170688900_ref1","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1124\/pr.114.009464","article-title":"International Union of Basic and Clinical Pharmacology. 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The parathyroid hormone receptors\u2013family B G protein-coupled receptors","volume":"67","author":"Gardella","year":"2015","journal-title":"Pharmacol Rev"},{"issue":"9","key":"2024103012170688900_ref2","doi-asserted-by":"publisher","first-page":"3365","DOI":"10.1210\/jcem.83.9.5243","article-title":"A homozygous inactivating mutation in the parathyroid hormone\/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia","volume":"83","author":"Zhang","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2024103012170688900_ref3","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/BF00572767","article-title":"A new familial skeletal dysplasia with severely retarded ossification and abnormal modeling of bones especially of the epiphyses, the hands, and feet","volume":"141","author":"Eiken","year":"1984","journal-title":"Eur J 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