{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T22:17:01Z","timestamp":1757542621691,"version":"3.40.5"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The <jats:italic>GNAS<\/jats:italic> gene (OMIM#139320), located on chromosome 20q13.2, encodes for the alpha\u2010subunit of the stimulatory signaling protein, Gs\u03b1 protein. <jats:italic>GNAS<\/jats:italic> variants with inactivating properties are associated with Albright's hereditary osteodystrophy (AHO) and when maternally inherited, pseudohypoparathyroidism 1a (OMIM#103580), which includes multiple hormone resistance. In this clinical report we describe a novel <jats:italic>GNAS<\/jats:italic> variant, c.159A&gt;G, p.K53N, in an individual with features consistent with AHO and pseudohypoparathyroidism 1a and its segregation through multiple maternal relatives, including two genotype positive maternal first cousins who also display features classic for AHO. The proband developed unique features including cardiomyopathy which required a heart transplant at 5\u2009years old and immune dysregulation resulting in multisystem organ failure and ultimately, death at the age of 18\u2009years. Additional investigations exploring alternative explanations for the proband's presentation were pursued including whole genome sequencing which was negative. We postulate that the atypical features seen in the proband may have resulted from dysregulated Gs\u03b1 signaling in cardiac tissue. Future studies are needed to explore the properties of the K53N <jats:italic>GNAS<\/jats:italic> variant and this proposed mechanism.<\/jats:p>","DOI":"10.1002\/ajmg.a.62726","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T07:22:51Z","timestamp":1648538571000},"page":"2147-2152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel <scp><i>GNAS<\/i><\/scp> variant presents with disorders of <scp><i>GNAS<\/i><\/scp> inactivation and cardiomyopathy"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1911-1846","authenticated-orcid":false,"given":"Emily","family":"Shelkowitz","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Section of Clinical Genetics and Metabolism University of Colorado  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine M.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Endocrinology University of Colorado  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tonya","family":"Jones","sequence":"additional","affiliation":[{"name":"Center for Genetics at Saint Francis Hospital  Tulsa Oklahoma USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie J.","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Cardiology University of Colorado  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi J. L.","family":"Meeks","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Clinical Genetics and Metabolism University of Colorado  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109765"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/PEC.0b013e31829861a3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv195"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.2.101"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22265"},{"issue":"2","key":"e_1_2_9_7_1","first-page":"000993","article-title":"Pseudohypoparathyroidism and cardiomyopathy: A case report with a new perspective on the cardiovascular\u2010endocrine axis with respect to calcium homeostasis","volume":"6","author":"Fasih A.","year":"2019","journal-title":"European Journal of Case Reports in Internal Medicine"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21438"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/371164a0"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1997.272.1.H585"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.05.032"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22696"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59097"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.11.018"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(05)68002-7"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.119578"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00627.2013"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-015-0268-x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.11.835"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951113002023"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62726","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62726","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62726","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T08:56:12Z","timestamp":1692867372000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,29]]},"references-count":22,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/ajmg.a.62726"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62726","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2022,3,29]]},"assertion":[{"value":"2021-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}