Figure 5
pSNMs detected in DS1-II-2 and DS2-I-1 in the gene SCN1A and transmitted to their respective child with Dravet syndrome as a heterozygous mutation. (A) The two non-synonymous mutations are highlighted by red arrows on transmembrane structure of the sodium channel encoded by SCN1A. These mutations alter residues located at the ends of the loop structures in domains III and IV, adjacent to previously known pathogenic mutations in Dravet syndrome which are shown here as small circles with different colors representing different mutation type. (B) The parent-to-offspring transmission model is illustrated for c.5003C→G pSNM. In the mother, the mutant allele generated by postzygotic mutations is present in a proportion of the cell population and identified by our pipeline as a pSNM. The mosaicism apparently affected germ cells, and thus the offspring had a chance to inherit the mutation during gametogenesis and fertilization, leading to the heterozygous genotype.
