Figure 2

Segregation of C2CD3 mutations and protein ideogram indicating location of variants.

(a) C2CD3 variants present in the parents and affected individuals in the reported family. Sequence reads highlight genotype for variants identified by Sanger sequencing under each individual. Arrows denote missense mutation, dotted lines denote deletion site. Note that the sequence scan for the c.195G > C mutation shows the reverse strand sequence; the c.1429delA mutation is shown on the forward strand. (b) Human C2CD3 protein schematic showing mutations detected in the present study (red lines, top), mutations reported in previously reported OFDS cases²⁰ (dotted lines, bottom) and mouse C2cd3 alleles C2Cd3^Gt (Gt) and Hearty (Hty) (dotted lines, bottom). Note the C2cd3^Gt mutation is predicted to result in a truncated protein encoding the N-terminal 161 amino acids only; aberrant splicing in Hty leads to proteins either truncated at amino acid 235, or with small in-frame deletions in the same region^20,21. C2: canonical C2 domains, C2CD3N: non-canonical globular C2 domain²⁹.