Droplet digital PCR as a first-tier molecular diagnostic tool for focal cortical dysplasia type II.

Abstract

We read with interest the recent article by Pirozzi et al.1 demonstrating the utility of droplet digital PCR (ddPCR) for the molecular genetic diagnosis of focal malformations of cortical development (FMCD) including focal cortical dysplasia (FCD), hemimegalencephaly (HMEG) and dysplastic megalencephaly (DMEG). By targeting six recurrent variants in MTOR, PIK3CA and AKT3, Pirozzi et al.1 achieved a diagnostic rate of 24.2% for FCD (8 of 33 individuals) and 81.8% for HMEG/DMEG (9 of 11 individuals). Our research lab has also implemented a similar strategy to rapidly screen for recurrent variants in FCD samples, with favourable outcomes. As a result, ddPCR has become a routine research genetic testing method for FCD samples collected from the Epilepsy Surgery Program at the Royal Children’s Hospital, Melbourne. The purpose of this letter is to provide supporting evidence for the article by Pirozzi et al.,1 and to advocate for the implementation of ddPCR as a first-tier molecular diagnostic tool for FMCD, particularly FCD Type II (FCDII). We present the research findings generated at the Royal Children’s Hospital, Melbourne, and discuss how this approach can be further improved and utilized as a research or clinical grade diagnostic tool.