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Endocrine Abstracts (2019) 63 OC7.4 | DOI: 10.1530/endoabs.63.OC7.4

ECE2019 Oral Communications Endocrine Connections 1 (5 abstracts)

Non-invasive detection of GNAS mutations causing McCune-Albright Syndrome with ddPCR on whole blood or circulating DNA

Pauline Romanet 1 , Pascal Philibert 2 , Frédéric Fina 3 , Thomas Cuny 1 , Rachel Reynaud 1 , Françoise Paris 2 & Anne Barlier 1

1Aix Marseille Univ, Marseille, France; 2CHU Montpellier, Montpellier, France; 3APHM, Marseille, France.

Context: Postzygotic activating mutations in GNAS are responsive for fibrous dysplasia (FD) and McCune-Albright Syndrome (MAS). MAS is a rare disease associating fibrous dysplasia, to skin pigmentation and endocrine disorders. The classic genetic non-invasive methods are insufficiently sensitive to detect GNAS mutation, due to a low level of mosaicism in blood. Early diagnostic should allow a follow-up and a therapeutic choice adapted to the MAS context in order to reduce the complications and optimize the quality of life. The development of a sensitive and non-invasive test represents a significant step forward for an early diagnosis improving further monitoring of the patients.

Patients and Methods: We used an ultrasensitive quantitative PCR using digital droplet PCR (ddPCR) technology for the detection of GNAS mutations. First we did a validation study of assays targeting the R201C and R201H mutations on 18 patients previously characterized by nested-PCR method. Then we tested the DNA of naive patients presented FD or MAS, after extraction from whole blood and from plasma, i.e. circulating cell-free DNA (ccfDNA).

Results: Seventeen patients presented 1 to 3 FD/MAS lesions were included. Using ddPCR, we detect GNAS mutations in whole blood DNA from 7/12 patients; and the combined analyses on both whole blood DNA and ccfDNA led to a FD/MAS molecular diagnosis in 4/5 patients.

Conclusions: We demonstrated the relevance of using ddPCR to screen for GNAS mutations in patients with at least one feature of FD/MAS, with considerable benefits in terms of precision, acceptability and cost-effectiveness.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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