Co-existence of ABCB11 and DCDC2 disease: Infantile cholestasis requires both next-generation sequencing and clinical-histopathologic correlation

摘要

a, b The homozygous missense variant c.1213T>C changes cysteine-405 to arginine in human. Cysteine-405 corresponds to serine-373 in murine P-glycoprotein. The structure of murine P-glycoprotein serves to model the identified substitution with the larger, charged and hydrophilic arginine. The mutated residue lies in interhelical domain 6, close to nucleotide-binding domain 1. Distances to glutamine-155 in interhelical domain 1 (dark blue) and serine-905 in interhelical domain 4 (green) are altered, suggesting that this variant may impair substrate entry into BSEP at the transmembrane domain: nucleotide-binding domain junction. c Sequence chromatograms, DCDC2, and ABCB11 of patient and his parents.