{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:10:49Z","timestamp":1791807049542,"version":"4.3.4"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Bone &amp; Mineral Res"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fibrous dysplasia\/McCune\u2010Albright syndrome (FD\/MAS) is a rare mosaic bone and endocrine disorder. Although most variants affect the\n                    <jats:italic>GNAS<\/jats:italic>\n                    R201 codon, obtaining a genetic diagnosis is difficult because not all cells harbor the variant, and an invasive biopsy may be required. We explored the presence of\n                    <jats:italic>GNAS<\/jats:italic>\n                    p.R201 variants in blood circulating cell free DNA (ccfDNA) using sensitive techniques of digital droplet polymerase chain reaction (PCR) (ddPCR) and competitive allele\u2010specific TaqMan PCR (castPCR) in an effort to improve the genetic diagnosis of FD\/MAS. We isolated ccfDNA from the plasma of 66 patients with a wide range of disease severity and performed both ddPCR and castPCR mutation analysis to search for\n                    <jats:italic>GNAS<\/jats:italic>\n                    p.R201H or R201C variants. We detected R201 variants in ccfDNA samples of 41 of 66 (62.1%) patients by either castPCR or ddPCR, and 45 of 66 (68.2%) of patients if the techniques were combined. Variant detection was more likely in patients with more severe disease. Skeletal disease burden score (SBS) was significantly higher in patients who had detectable variants, and SBS was a predictor of variant allele frequency. By ddPCR analysis, patients aged \u226430\u2009years had higher detection rates, and higher variant allele frequencies, independent of disease burden. We detected variant DNA in only one patient with monostotic FD by ddPCR only. In summary, we have demonstrated that ccfDNA containing variant\n                    <jats:italic>GNAS<\/jats:italic>\n                    can be isolated from the plasma of patients with FD\/MAS and that ddPCR and castPCR methods have similar variant detection rates. This methodology represents an important potential advancement in diagnosis for patients with FD\/MAS, especially those younger than 30\u2009years or with more severe disease. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.\n                  <\/jats:p>","DOI":"10.1002\/jbmr.4766","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:29:56Z","timestamp":1672705796000},"page":"443-450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Identification of\n                    <scp>\n                      <i>GNAS<\/i>\n                    <\/scp>\n                    Variants in Circulating\n                    <scp>Cell\u2010Free DNA<\/scp>\n                    from Patients with Fibrous Dysplasia\/\n                    <scp>McCune<\/scp>\n                    Albright Syndrome"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-5299","authenticated-orcid":false,"given":"Kelly L.","family":"Roszko","sequence":"first","affiliation":[{"name":"Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Guthrie","sequence":"additional","affiliation":[{"name":"Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobai","family":"Li","sequence":"additional","affiliation":[{"name":"Biostatistics and Clinical Epidemiology Service NIH Clinical Center, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3676-7644","authenticated-orcid":false,"given":"Michael T.","family":"Collins","sequence":"additional","affiliation":[{"name":"Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-9780","authenticated-orcid":false,"given":"Luis F.","family":"de Castro","sequence":"additional","affiliation":[{"name":"Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M.","family":"Boyce","sequence":"additional","affiliation":[{"name":"Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"GeneReviews(\u00ae)","author":"Boyce 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