Fig. 1.

Identification of novel compound heterozygous variants at CUBN using ES in two families. A Schematic to scale overview of the genomic CUBN structure and the variants (c.6796C > T and c.4397G > A, c.6821 + 3A > G and c.5153_5154delCT) were mapped. And then the variants were further confirmed by Sanger sequencing in the two probands’ families. B Phylogenetic analysis of CUBN. The proportion of replicate trees in which the associated taxa clustered together in the bootstrap test were shown next to the branches. C Pedigree of the probands’ family with the novel compound heterozygous variants in CUBN gene. D Crystal structures of CUB domain 9, 11 and 16 of Cubilin protein oligomers in the oligomerized conformation. The mutated residues (p.C1466Y, p.S1718X and p.R2266X) were marked with Dotted circles. E Schematic of the Cubilin protein domains. The novel variants were marked with black arrows