Additional file 1: Fig. S1. Demonstrates how CRISPR/ cas9 genome editing induces exon skipping in X.tropicalis. Fig. S2. Shows the eye (a target organ) and the remainder of the crispant tadpole are equally mosaic. Fig. S3. Confirms that disruption to copb1 exon 8 in X.tropicalis mirrors syndromic hallmarks. Fig. S4. Supplemental figure demonstrates a more exaggerated phenotype in tadpoles injected with CRISPR/cas9 targeting exon 3, copb1. Fig. S5. Illustrates Xenopus anatomy and the significant reduction in brain size seen in transgenic tadpoles. Fig. S6. Shows there is no difference in localisation of wild type beta COP versus the Family 2 variant beta COP. Table S1. Details the immunodeficiency investigations performed in Family 2. Table S2. Details other shared homozygous variants identified in both probands of Family one.