Utility of droplet digital polymerase chain reaction for studying somatic mosaicism:brain malformations and beyond

摘要

Somatic variants and how to find them:One major challenge in studying somatic mosaicism is the low abundance of potentially pathogenic somatic variant(s).Unlike inherited germline variants,which are essentially present in all cells,pathogenic somatic variants only exist in a subset of cells and may be present at very low (<1%)variant allele frequency (VAF).Despite the low VAF,these somatic variants are disease-relevant and considered pathogenic.In the context of focal brain malformations,which constitute a frequent cause of drug-resistant focal epilepsy,a pathogenic somatic mammalian ta rget of rapamycin (MTOR)variant with a VAF of 0.3%has been described(Baldassari et al.,2019).The identification of pathogenic somatic variants has importa nt implications both clinically and biologically.