Fig. 2
From: Clinical relevance of targeted exome sequencing in patients with rare syndromic short stature
Visual findings, radiographic skeletal survey, and genetic analysis in patient K2 with Hajdu–Cheney syndrome. a, b Short and broad digits were observed; c cone-shaped distal phalanges due to peripheral acrolysis is indicated by yellow arrows; d wormian bones are marked by yellow arrows in the lambdoidal suture; e lumbar scoliosis is marked by yellow arrows; f malocclusion and biconcave vertebra bodies marked by yellow arrows. Two novel heterozygous variants in the NOTCH2 gene (NM_024408.3). g, h Sanger sequencing confirmed two de novo novel variants, c.2816C>T (p.P939L) and c.5471G>A (p.R1824H), in NOTCH2 in patients K2 and K15, respectively, shown by the red arrow. P939 located on EGF-like repeats and R1824H on ankyrin repeat domain residues are conserved among species, shown in the dark square box. Sequences were aligned using blastp [https://blast.ncbi.nlm.nih.gov/]; i, j wild-type and mutant residues (p.P939L and p.R1824H) in the NOTCH2 protein are shown in light-green and are also represented as sticks alongside the surrounding residues, indicating any type of interaction. Purple dots represent metal complex interactions with a surrounding residue. Orange dots represent weak hydrogen bonds with a surrounding residue. The crystal structure of the domain from wild-type NOTCH2 was generated by SWISS-MODEL [https://swissmodel.expasy.org/] and depicted as a cartoon representation. All structural images were generated using PyMOL (https://pymol.org/)