Novel Large-scale Deletion (whole Exon 7) in the ABCC2 Gene in a Patient with the Dubin-Johnson Syndrome

• Published in: Drug metabolism and pharmacokinetics Vol. 24; no. 5; pp. 464 - 468
• Main Authors: Kanda, Daisuke, Takagi, Hitoshi, Kawahara, Yasutsugu, yata, Yutaka, Takakusagi, Tomofumi, Hatanaka, Takeshi, Yoshinaga, Teruo, Iesaki, Keigo, Kashiwabara, Kenji, Higuchi, Tsugio, Mori, Masatomo, Hirota, Takeshi, Higuchi, Shun, Ieiri, Ichiro
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2009
• Subjects: ABCC2; Aged; Base Sequence; Dubin-Johnson syndrome; Female; Humans; Jaundice, Chronic Idiopathic - genetics; large-scale deletion; Molecular Sequence Data; MRP2; Multidrug Resistance-Associated Proteins - genetics; Polymorphism, Single Nucleotide; Sequence Deletion; single nucleotide polymorphism; large-scale deletion; Dubin-Johnson syndrome; MRP2; ABCC2; single nucleotide polymorphism
• ISSN: 1347-4367; 1880-0920
• DOI: 10.2133/dmpk.24.464

The Dubin-Johnson syndrome (DJS) is an inherited liver disorder characterized by conjugated hyperbilirubinemia and caused by ABCC2 gene mutations resulting in deficiency of multidrug resistance associated-protein 2 (MRP2) function. A 76-year-old woman with serious jaundice was referred to our hospital. She was clinically diagnosed with DJS with hepatic congestion, due to constrictive pericarditis. We analyzed all exons and exon-intron junctions of the ABCC2 gene by DNA sequencing and identified a new large-scale deletion, 1008bp, including the whole exon 7, as homozygosity. Some mutations in the ABCC2 gene associated with splicing errors have been reported in intronic regions; however, this is a new type of large-scale deletion detectable in the genomic DNA sequence. Severe hyperbilirubinemia is rare in patients with constrictive pericarditis and this case suggests that MRP2 may play a crucial role in compensating for the serum bilirubin in congestive hepatopathy.