{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T16:35:05Z","timestamp":1773160505553,"version":"3.50.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Science Foundation for Young Scientists of China","award":["81900722"],"award-info":[{"award-number":["81900722"]}]},{"name":"the Project of Shanghai Municipal Science and Technology Commission","award":["20MC1920400"],"award-info":[{"award-number":["20MC1920400"]}]},{"name":"the Project of Shanghai Municipal Science and Technology Commission","award":["20MC1920400"],"award-info":[{"award-number":["20MC1920400"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Endocr Disord"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The <jats:italic>GNAS<\/jats:italic> gene on chromosome 20q13.3, encodes the alpha-subunit of the stimulatory G protein, which is expressed in most tissues and regulated through reciprocal genomic imprinting. Disorders of <jats:italic>GNAS<\/jats:italic> inactivation produce several different clinical phenotypes including pseudohypoparathyroidism (PHP), pseudopseudohypoparathyroidism (PPHP), progressive osseous heteroplasia (POH), and osteoma cutis (OC). The clinical and biochemical characteristics overlap of PHP subtypes and other related disorders presents challenges for differential diagnosis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We enrolled a total of 11 Chinese children with PHP in our study and analyzed their clinical characteristics, laboratory results, and genetic mutations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Among these 11 patients, nine of them (9\/11) presented with resistance to parathyroid hormone (PTH); and nine (9\/11) presented with an Albright\u2032s hereditary osteodystrophy (AHO) phenotype. <jats:italic>GNAS<\/jats:italic> abnormalities were detected in all 11 patients, including nine cases with <jats:italic>GNAS<\/jats:italic> gene variations and two cases with <jats:italic>GNAS<\/jats:italic> methylation defects. These <jats:italic>GNAS<\/jats:italic> variations included an intronic mutation (c.212\u2009+\u20093_212\u2009+\u20096delAAGT), three missense mutations (c.314C\u2009&gt;\u2009T, c.308\u00a0T\u2009&gt;\u2009C, c.1123G\u2009&gt;\u2009T), two deletion mutations (c.565_568delGACT*2, c.74delA), and two splicing mutations (c.721\u2009+\u20091G\u2009&gt;\u2009A, c.432\u2009+\u20091G\u2009&gt;\u2009A). Three of these mutations, namely, c.314C\u2009&gt;\u2009T, c.1123G\u2009&gt;\u2009T, and c.721\u2009+\u20091G\u2009&gt;\u2009A, were found to be novel. This data was then used to assign a <jats:italic>GNAS<\/jats:italic> subtype to each of these patients with six cases diagnosed as PHP1a, two cases as PHP1b, one as PPHP, and two as POH.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Evaluating patients with PTH resistance and AHO phenotype improved the genetic diagnosis of <jats:italic>GNAS<\/jats:italic> mutations significantly. In addition, our results suggest that when <jats:italic>GNAS<\/jats:italic> gene sequencing is negative, <jats:italic>GNAS<\/jats:italic> methylation study should be performed. Early genetic detection is required for the differential diagnosis of <jats:italic>GNAS<\/jats:italic> disorders and is critical to the clinician\u2019s ability to distinguish between heterotopic ossification in the POH and AHO phenotype.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12902-022-00941-8","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T22:03:36Z","timestamp":1647468216000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Evaluating the variety of GNAS inactivation disorders and their clinical manifestations in 11 Chinese children"],"prefix":"10.1186","volume":"22","author":[{"given":"Guoying","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongnian","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiumin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"941_CR1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s40618-016-0588-4","volume":"40","author":"O Tafaj","year":"2017","unstructured":"Tafaj O, J\u00fcppner H. 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Informed consent for publication was obtained from all of the families of individual participants included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the journal editor.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflicts of interest related. The authors state that the material is original, has not been previously published, and has not been submitted for publication elsewhere while under consideration.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}