fig4

Figure 4. Genetic test results for the patient and pathogenicity analysis of the variant. (A) Pedigree of the family: the black arrowhead indicates the proband. The proband is homozygous for c.680T>C in the ABCG8 gene, and his parents and sisters are all heterozygotes; (B) Sanger sequencing of the ABCG8 gene in the family; red arrowheads indicate the variant c.680T>C in the ABCG8 gene; (C) Conservation analysis of the affected residue across species revealed strong evolutionary preservation of this amino acid position; (D) Computational modeling predicts that this missense variant disrupts a critical hydrogen bond between Leu227 and Ile223; (E) An online prediction indicates that this variant may cause abnormal mRNA splicing. The blue regions correspond to exons, whereas the light-colored areas indicate a 71-bp deletion at the 3’ end of exon 5.