[Analysis a patient with Dubin-Johnson syndrome due to a rare c.4120C>T nonsense variant of ABCC2 gene].

OBJECTIVE

To report on a case of Dubin-Johnson syndrome (DJS) with a rare ABCC2 nonsense variant.

METHODS

Clinical, histopathological, MRP2 immunohistochemical, and whole-exome sequencing findings were retrospectively analyzed. This study was approved by the Medical Ethics Committee of Taizhou People's Hospital (Ethics No.: 20250522).

RESULTS

A 58-year-old woman with mild conjugated hyperbilirubinemia with normal aminotransferases and cholestatic enzymes, and black liver was incidentally discovered during laparoscopy. Histology showed melanin-like pigment deposition, and MRP2 immunohistochemistry was negative. Two heterozygous ABCC2 variants, namely c.2063T>C and c.4120C>T, were identified. The previously unreported nonsense variant c.4120C>T was predicted to truncate the MRP2 protein within the second nucleotide-binding domain (NBD2). Retrospective analysis of SLCO1B1 and SLCO1B3 had not identified any pathogenic/likely pathogenic variants for Rotor syndrome. As family samples were unavailable, the allelic phase of the two ABCC2 variants could not be determined.

CONCLUSION

The clinical, histopathological, and immunohistochemical findings in the woman had supported the diagnosis of DJS. The two unphased heterozygous ABCC2 variants provided supportive molecular evidence, but confirmation of biallelic involvement requires further segregation or phase analysis.