{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:03:01Z","timestamp":1775142181491,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100030988","name":"The Miriam Hospital","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100030988","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>McCune\u2013Albright Syndrome (MAS) is a rare mosaic disorder caused by somatic activating mutations of the GNAS gene, resulting in constitutive Gs\u03b1 signaling and a broad spectrum of clinical phenotypes. The syndrome typically presents with fibrous dysplasia (FD) of bone, caf\u00e9-au-lait macules, and endocrinopathies such as gonadotropin-independent precocious puberty, hyperthyroidism, and\/or growth hormone excess. FD, which characterizes the skeletal phenotype, results in the replacement of normal bone with disorganized fibro-osseous tissue, often leading to pain, deformities, and increased risk of fractures. This review discusses the following: 1. The molecular biology of the GNAS locus and its relation to the pathophysiology of FD\/MAS; 2. The skeletal manifestations of FD\/MAS; 3. Bone biomechanics and organizational skeletal aberrations observed in FD\/MAS; and 4. Current and future therapeutic strategies for patients with FD\/MAS. While there is much current literature available regarding FD\/MAS, this review specifically aims to outline core understandings and summarize some of the latest investigations into the genotypic and phenotypic foundations of the disorders, while shedding new light on the biomechanical aberrations observed in skeletal structure within them and comparing them to those observed in related disease processes such as osteoporosis and Paget\u2019s disease.<\/jats:p>","DOI":"10.3390\/genes16111360","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T11:47:27Z","timestamp":1762775247000},"page":"1360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The GNAS Gene: Fibrous Dysplasia, McCune\u2013Albright Syndrome, and Skeletal Structure and Function"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7122-2423","authenticated-orcid":false,"given":"Jake Louis","family":"Littman","sequence":"first","affiliation":[{"name":"School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2127-6239","authenticated-orcid":false,"given":"Wentian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4832-2352","authenticated-orcid":false,"given":"Noah","family":"Feder","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amr","family":"Kaadan","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4798-0424","authenticated-orcid":false,"given":"Ali","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0745-2267","authenticated-orcid":false,"given":"Roy K.","family":"Aaron","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1001\/archpedi.1937.01980040110009","article-title":"Osteodystrophia Fibrosa: Report of a Case in Which the Condition Was Combined with Precocious Puberty, Pathologic Pigmentation of the Skin and Hyperthyroidism, with a Review of the Literature","volume":"54","author":"McCune","year":"1937","journal-title":"Am. 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