Fig. 4.

Families solved with variants that represented interpretation challenges. A Pedigree of family F3612 with three stillbirths all presenting with microcephaly and skeletal dysplasia phenotypes. B and C X-ray and clinical image of an affected individual (IV:4) highlighting radial ray deficiency. D Pedigree of family F5543 with an affected baby with polycystic kidney disease. E Clinical image of individual (IV:5) with Potter facies and swollen abdomen. F) Pedigree of family F5349 referred to us with two affected cousins both presenting with severe limb malformations. G and H Clinical images of affected individual (IV:6) with absent radius and hypoplasia of the ulna. I X-ray images of the right hand of affected individual (IV:6) highlighting absent radial ray and bowed ulna. J Pedigree of family F5993 with two brothers affected with retinal dystrophy. K (top) Genomic representation of identical haplotypes between two families homozygous for the same STX3 variant. HomozygosityMapper shows that they map to a single locus on Chr.13; (bottom) schematic representation of two STX3 transcripts, one where the variant is a frameshift insertion and the other (MANE select) as deep intronic. L Pedigree of family F8602 with two cousins affected with vein of Galen malformation. M Brain ultrasound imaging of individual (IV:2) showing dilatation of the veins of Galen. N Pedigree of family F7887 with NDD. O Pedigree of family F8544 with two siblings and a cousin affected with NDD. Illustrations at the bottom of panel (K) were created using BioRender.com