Figure 2.

Pedigrees, MAB21L1 mutation segregation patterns and mutation localisation on cDNA and protein level. (A) Pedigrees of four families harbouring biallelic MAB21L1 loss-of function variants identified by ES. In total, nine affected individuals were identified. Wildtype alleles are indicated by ‘+’, alleles carrying identified variants with ‘ -’. (B) Visualisation of the MAB21L1 gene and COFG associated alleles identified by us as well as the previously identified MAB21L1 allele Bruel et al.¹² (C) Schematic overview of localisations of COFG alleles on protein level. (D) Computational structural model of human MAB21L1, Visualisation of the aminoacid change identified in family 2 and predicted effect on protein folding/structure and evolutionary conservation of the mutated position among species. The variant is predicted to disrupt hydrogen bond formation within the alpha-helix structure, disrupting the protein secondary structure. COFG, Cerebello-Oculo-Facio-Genital; ES, exomic sequencing.