Identification of GNAS Variants in Circulating Cell‐Free DNA from Patients with Fibrous Dysplasia/McCune Albright Syndrome

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare mosaic bone and endocrine disorder. While most variants affect the GNAS R201 codon, obtaining a genetic diagnosis is difficult because not all cells harbor the variant, and an invasive biopsy may be required. The study explored the presence of GNAS p. Skeletal disease burden score (SBS) was significantly higher in patients with detectable variants, and SBS was a predictor of variant allele frequency. By ddPCR analysis, patients aged ≤30 had higher detection rates and variant allele frequencies independent of disease burden. The study detected the variant DNA in only one patient with monostotic FD by ddPCR. The study findings demonstrated that ccfDNA containing variant GNAS 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 diagnosing patients with FD/MAS, especially those younger than 30 or with more severe diseases.