Figure 4. These are illustrations of both the exon structure and a schematic of the Protocadherin-21 (PCDH21) protein with indications of the location of the two deletions. Sequence alignments demonstrate the conservation of both amino-acid positions across several species. Panel A: PCDH21 exon structure as derived from ensembl: the exons are colored according to domain structure, and, as illustrated in Panel B, with asterisks to denote the location of the novel deletions. Panel B is a schematic of the cellular domain structure derived from UniProt (created using Adobe Illustrator-Adobe Systems Inc.) with the protein numbers corresponding to each of the structural domains. Panel C is an sequence alignment created using PipeAlign for PCDH21 mutation p.G113fsX1, that was identified in family 1, and shows that there is a high level of conservation at this amino acid position-except for species Danio rerio. Panel D is a further alignment around the site of the PCDH21 deletion p.G487fsX20, identified in family 2, demonstrating a high level of conservation at this amino acid position and therefore providing evidence of the likely deleterious effect of this variant.