Mosaic ratio quantification of isochromosome 12p in Pallister-Killian syndrome using droplet digital PCR

Katsunori Fujiki; Katsuhiko Shirahige; Maninder Kaur; Matthew A Deardorff; Laura K Conlin; Ian D Krantz; Kosuke Izumi

doi:10.1002/mgg3.200

Mosaic ratio quantification of isochromosome 12p in Pallister-Killian syndrome using droplet digital PCR

Mol Genet Genomic Med. 2016 Jan 20;4(3):257-61. doi: 10.1002/mgg3.200. eCollection 2016 May.

Authors

Katsunori Fujiki¹, Katsuhiko Shirahige¹, Maninder Kaur², Matthew A Deardorff³, Laura K Conlin⁴, Ian D Krantz³, Kosuke Izumi¹

Affiliations

¹ Research Center for Epigenetic Disease, Institute for Molecular and Cellular Biosciences The University of Tokyo Tokyo Japan.
² Division of Human Genetics The Children's Hospital of Philadelphia Philadelphia Pennsylvania.
³ Division of Human GeneticsThe Children's Hospital of PhiladelphiaPhiladelphiaPennsylvania; The Perelman School of Medicine at The University of PennsylvaniaPhiladelphiaPennsylvania.
⁴ The Perelman School of Medicine at The University of PennsylvaniaPhiladelphiaPennsylvania; Department of Pathology and Laboratory MedicineThe Children's Hospital of PhiladelphiaPhiladelphiaPennsylvania19104.

Abstract

Background: Pallister-Killian syndrome (PKS) is a prototypic mosaic aneuploidy syndrome caused by mosaic supernumerary marker isochromosome 12p. Cells possessing the isochromosome 12p rapidly diminish after birth in the peripheral blood, often necessitating a skin biopsy for diagnosis. Therefore, a genomic testing that is capable of detecting low percent mosaic isochromosome 12p is preferred for the diagnosis of PKS.

Methods: The utility of the droplet digital PCR system in quantifying the mosaic ratio of isochromosome 12p in PKS was evaluated.

Results: Droplet digital PCR was able to precisely quantify isochromosome 12p mosaic ratio, and copy number measured by droplet digital PCR was correlated well with that of fluorescence in situ hybridization analysis.

Conclusion: Droplet digital PCR should be considered as an effective tool for both clinical and research analytics to precisely quantify mosaic genomic copy number alterations or mosaic mutations.

Keywords: Copy number variation; isochromosome 12p; mosaicism.