Mixed Dubin-Gilbert Syndrome: A Compound Heterozygous Phenotype of Two Novel Variants in ABCC2 Gene

• Published in: Chinese medical journal Vol. 130; no. 8; pp. 1003 - 1005
• Main Authors: Jiang, Jun, Wang, Hua-Gui, Wu, Wei-Li, Peng, Xiang-Xin
• Format: Journal Article
• Language: English
• Published: China Medknow Publications and Media Pvt. Ltd 20.04.2017; Lippincott Williams & Wilkins Ovid Technologies; The Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China%Department of Infectious Diseases, China-Japan Friendship Hospital, Beijing 100029, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer
• Subjects: ABCC2 Gene; Dubin–Johnson Syndrome; Gilbert's Syndrome; Hyperbilirubinemia; UGT1A1 Gene; Adult; Care and treatment; Case studies; Clinical Practice; Diagnosis; Female; Gene mutation; Genetic counseling; Genomes; Genomics; Gilbert Disease - genetics; Gilbert's disease; Glucuronosyltransferase - genetics; Hospitals; Humans; Hyperbilirubinemia - genetics; Jaundice, Chronic Idiopathic - genetics; Laboratories; Multidrug Resistance-Associated Proteins - genetics; Mutation; Mutation - genetics; Gilbert's Syndrome; Hyperbilirubinemia; Dubin-Johnson Syndrome; UGT1A1 Gene; ABCC2 Gene
• ISSN: 0366-6999; 2542-5641
• DOI: 10.4103/0366-6999.204108

[1] Dubin-Johnson syndrome (DJS, MIM #237500) is characterized by fluctuating mild, predominantly conjugated hyperbilirubinemia and is caused by mutations in the ATP-binding cassette subfamily C member 2 gene (ABCC2). Physical examination after admission to our hospital showed that she was febrile, with normal blood pressure and heart rate, and of height 160 cm and weight 50 kg. Sequencing of polymerase chain reaction-amplified DNA of the entire coding regions and exon-intron boundaries of UGT1A1 (NM_000463.2) and ABCC2 (NM_000392.3) in the patient revealed two novel mutations [Figure 1]c: a heterozygous in-frame insertion deletion mutation c.4712_4720delinsGGCCCACAG in exon 31, inherited from her father, and a heterozygous mutation p.I448V in exon 10, inherited from the mother. Based on PolyPhen-2 (Harvard Medical School, Boston, Massachusetts, USA), the I448V mutation was found to be "probably damaging" to protein structure and function, with a score of 0.999. Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome.