Using Digital Droplet Polymerase Chain Reaction to Detect the Mosaic GNAS Mutations in Whole Blood DNA or Circulating Cell-Free DNA in Fibrous Dysplasia and McCune-Albright Syndrome

Pauline Romanet; Pascal Philibert; Frédéric Fina; Thomas Cuny; Catherine Roche; L'houcine Ouafik; Françoise Paris; Rachel Reynaud; Anne Barlier

doi:10.1016/j.jpeds.2018.09.070

Using Digital Droplet Polymerase Chain Reaction to Detect the Mosaic GNAS Mutations in Whole Blood DNA or Circulating Cell-Free DNA in Fibrous Dysplasia and McCune-Albright Syndrome

J Pediatr. 2019 Feb:205:281-285.e4. doi: 10.1016/j.jpeds.2018.09.070. Epub 2018 Nov 13.

Authors

Pauline Romanet¹, Pascal Philibert², Frédéric Fina³, Thomas Cuny⁴, Catherine Roche⁵, L'houcine Ouafik⁶, Françoise Paris⁷, Rachel Reynaud⁸, Anne Barlier⁵

Affiliations

¹ Aix Marseille Univ, APHM, INSERM, MMG, Hôpital de la Conception, Laboratory of Molecular Biology, Marseille, France. Electronic address: [email protected].
² Département de Biochimie et Hormonologie, Hôpital Lapeyronie, CHU Montpellier and Institut de Génétique Humaine, UMR 9002 CNRS-Université de Montpellier, France.
³ APHM, Unit of Technology Development, Laboratory of Medical Biology, Marseille, France.
⁴ Aix Marseille Univ, APHM, INSERM, MMG, Hôpital de la Conception, Department of Endocrinology APHM, Marseille, France.
⁵ Aix Marseille Univ, APHM, INSERM, MMG, Hôpital de la Conception, Laboratory of Molecular Biology, Marseille, France.
⁶ Marseille Univ, APHM, CNRS, INP UMR7259, Department of Biologic Oncology, Marseille, France.
⁷ CHU Montpellier, Molecular Biology Department, Montpellier; endocrinologie pédiatrique CHU Arnaud de Villeneuve Montpellier, France.
⁸ Aix Marseille Univ, APHM, INSERM, MMG, Hôpital La Timone Enfants, Pediatric Department, Marseille, France.

PMID: 30442414
DOI: 10.1016/j.jpeds.2018.09.070

Abstract

The GNAS postzygotic mosaic activating mutations involved in fibrous dysplasia and McCune-Albright syndrome (MAS) are not detectable in leukocytes by Sanger sequencing. Digital droplet polymerase chain reaction detects GNAS mutations in 7 of 12 patients (58.3%) suspected to have fibrous dysplasia/MAS from whole blood DNA, and in 4 of 5 patients (80%) from circulating cell-free DNA.

Keywords: detection; mosaic mutation; mosaicism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Cell-Free Nucleic Acids / blood
Cell-Free Nucleic Acids / genetics*
Child
Child, Preschool
Chromogranins / genetics*
Chromogranins / metabolism
DNA / blood
DNA / genetics*
DNA Mutational Analysis / methods
Female
Fibrous Dysplasia, Polyostotic / blood
Fibrous Dysplasia, Polyostotic / genetics*
GTP-Binding Protein alpha Subunits, Gs / genetics*
GTP-Binding Protein alpha Subunits, Gs / metabolism
Humans
Infant
Male
Middle Aged
Mutation*
Polymerase Chain Reaction / methods*
Young Adult

Substances

Cell-Free Nucleic Acids
Chromogranins
DNA
GNAS protein, human
GTP-Binding Protein alpha Subunits, Gs