Mosaicism in fibrous dysplasia/McCune-Albright Syndrome (FD/MAS): choosing the best tissue and technique

GNAS is a complex locus found in the long arm of chromosome 20. GNAS gene is located in this locus and activating somatic mutations give rise to fibrous dysplasia/McCune-Albright Syn-drome (FD/MAS). FD/MAS mutations occurs in mosaic, so more sensitive techniques than Sanger sequencing are needed to detect them. 40 patients were recruited and their clinical information was collected. To find genetic mosaicism, we sequenced GNAS gene of patients with clinical suspicion of FD/MAS, using both Sanger and Next-Generation Sequencing (NGS). After analyz-ing the results, a 25% of the patients presented a pathogenic variant. Most of them were identi-fied in affected tissue and not in blood. Besides, NGS demonstrated to detect more patients with mosaicism than Sanger sequencing. Regarding the principal clinical manifestations, data from various patients could not be collected. From that cases that information was available, clinic was heterogeneous and there was not a pattern. In conclusion, mosaicism must be taken into ac-count when genetic testing is done. Moreover, it is important to use sensitive techniques to de-tect low levels and to choose the right tissue to study. Finally, due to the low positive rate in genetics, FD/MAS should only be genetically tested when clinical diagnosis is uncertain.