Fig 3. Patient pedigrees and sequence chromatography of identified disease-associated variants.

Variants are denoted as M6, M7 and M8. (a) Family pedigree of patient 26007. (b) Sequence chromatography of heterozygous CDHR1 variant c.398C>G in patient (bottom), carrier mother (middle) and father (top). (c) Sequence chromatography of heterozygous CDHR1 variant c.439-17G>A in patient (bottom), mother (middle) and carrier father (top). (d) Predicted structure of CDHR1 reference protein (in blue) aligned to mutant CDHR1 (p.Pro133Arg) (in orange). The mutation is shown by magenta spheres and is localized within the first cadherin domain (white rectangle). (e) A zoomed image of the first cadherin domain of CDHR1 shows an additional beta-sheet (white arrow) close to the mutation (f) Family pedigree of patient 23530. (g) Agarose gel image of PRPF31 exon 7 PCR shows a larger band only in affected members indicating a duplication. C = Water control in PCR. (h) Comparison of predicted models of the PRPF31 reference protein sequence (i & v, in green), mutant PRPF31 (ii & vi, in magenta), alignment of reference and mutant PRPF31(iii & viii) and zoomed image of the alignment at the mutation site (iv & viii). An additional turn of the mutant in the coiled-coil domain is depicted in white. The first amino acid of the 11bp duplication is shown by a white arrow. “N” denotes the N-terminus of the protein.