ESPE Abstracts

Background: MAS is a rare disorder, this syndrome is classically characterized by a triad of physical signs: cafe-au-lait skin pigmentation(SP), fibrous bone dysplasia(FD), peripheral precocious puberty(PPP). In children, the most frequent initial presentation of MAS is PPP. MAS is caused by postzygotic activating mutations at the R201 codon of the GNAS gene, leading to a state of somatic mosaicium. In MAS patients, the frequency of mutations is expected to be generally low in clinically unaffected tissues such as peripheral blood leukocytes (PBL). Our aim to improve the mutation detection rate and quantify the presence of R201 GNAS mutations in PBL of MAS patients.

Methods: Compared with the PAP results, ddPCR techniques was used to search for R201 mutations in the DNA of blood from 73 MAS patients and 30 controls. The ability of ddPCR to provide quantitative data was tested in the dilution of wild –type, R201H,R201C cloned peripheral blood leukocytes.

Result: Compared with the PAP results, ddPCR showed that the analysis results of GNAS gene were obviously superior to the PAP method, especially for the non classic MAS, which was very difficult to be diagnosed clinically (77% and 9%), while the two generation sequencing could get a higher positive rate after the sequence of sequencing.

Conclusion: ddPCR techniques to the clinical screening of MAS molecular defects for the first time, and its efficiency is far higher than that of ordinary PCR. ddPCR is close to the classic and non classical positive rate of 70%, so it is currently in MAS.