Figure 1

DS cohort analyzed in the study and mDDPCR results identifying parental mosaicism in blood samples. (a) Description of the cohort analyzed in this study. A total of 719 DS affected families identified since 2005 were included. Sanger sequencing, panel NGS sequencing and MLPA detected SCN1A mutations from probands in 591 families. Peripheral blood samples from both parents are available for 242 of the families, and there are 8 probands among these families that inherited mutations from their parents according to the Sanger screening results. A total of 132 of the families provided blood samples and agreed to be included in the mDDPCR screening. TaqMan genotyping assays were able to be conducted for 112 families. (b) Overview of mDDPCR results that identified “de novo” mutations in families. The y-axis shows the maximum likelihood estimates of MAFs, and the error bars show the 95% binomial CIs calculated from the mDDPCR results. The probands have corrected MAFs between 40% and 60%, whereas the allele frequencies detected in the parents and negative controls were all under the detection limit. (c) Overview of MAFs measured in candidate parental mosaic families. Blood samples from family members are plotted. For each parental mosaic family, only one mosaic parent had an MAF 95% binomial CI between 50% and 0%. Blood samples from the non-mosaic parent and the negative control show MAFs of approximately 0%. (d) A representative result for parental mosaicism identified in family DS314 is shown. The PCR Sanger sequencing chromatogram, mDDPCR flow cytometry scatter plots and PASM raw IGV views and CI calculations after Bayesian modeling for the blood samples from the DS314 family are provided. Detailed mDDPCR flow cytometry scatter plots for all parental mosaic families are provided in Supplementary Fig. S7. (e) Histogram of the MAF distribution for parental blood samples from parental mosaic families.