Fig. 4: Identification of a homozygous deletion affecting the regulatory elements of DKK1 in four siblings with complex syndactyly.

a Clinical image of index individual of family F3029 showing syndactyly in feet. b X-ray images of the feet. c Photograph of the hands showing syndactyly. d X-ray of the hands. e Clinical image of the hands of a similarly affected sister with syndactyly of the middle finger. f Clinical image of the feet of the affected sister with syndactyly. g Representative illustration of DKK1 gene in mouse and human genomes. In mouse, the highlighted regions A, B, C, and D correspond to the four conserved non-coding elements (CNE25, CNE114, CNE190, and CNE195, respectively) identified downstream of DKK1 and are shown to drive its expression⁶². In humans, peaks corresponding to H3K27Ac and DNase-seq experiments are also highlighted in the deleted region identified in the affected members of this family. h Schematic representation of WT and Dkk1 knockout mice showing syndactyly in hands and feet. i RT-qPCR experiment measuring the transcript levels of DKK1 in the index individual and his affected sister compared to the control. Data show 60–80% reduction in DKK1 transcript levels. Data are presented as mean values +/− standard deviation (SD). Error bars represent the SD of three experiments. Panels (h) and (g) are created with BioRender.com.