case_images: PMC11790522_01
case_images: Patients and impact of the EP300 c.3671+5G>C variant. (A) Photographs illustrate the facial features typical of Subject #1 (left) and Subject #2 (right) at different ages. The images highlight limb features such as small hands and short toes. Both patients exhibit clinodactyly, not previously reported in literature for EP300 cases. (B) EP300 transcript analysis using cDNA extracted from blood. RT-PCR amplification targeting exons 19 through 21 revealed two bands. The band at approximately 300 bp corresponds to the wild-type transcript, found also in the control sample. The band around 200 bp indicates exon 20 skipping, as confirmed by gel extraction and Sanger sequencing. An additional band, marked by an asterisk, is likely a heteroduplex. The schematic on the right illustrates these splicing events. (C) The bioinformatics prediction of the NM_001429.4(EP300):c.3671+5_3671+8del variant in Subject #2 shows alteration in the splicing pattern. This four-base-pair deletion also induces a c.3671+5G>C change, likely impacting the splicing mechanism similarly. (D) A 3D reconstruction of the EP300 protein, generated through the Protein Homology/analogY Recognition Engine (PHYRE) version 2 (Supporting Information). The reconstruction illustrates the impact of the lack of exon 20. The absence of this exon results in the loss of amino acids within the RING domain, which encompasses exons 19, 20, and 21, subsequently altering the overall structure and function of the EP300 protein.
case_images: CGE-107-354-g001.jpg
case_images: PMC11790522_01_CGE-107-354-g001.jpg
case_images: cge14654-fig-0001
case_images: At 8 years old, her physical growth showed microcephaly, and echocardiography suggested possible dilation of the aortic bulb (Figure 1A and Supporting Information).