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.

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