Mutation analysis of the ABCC2 gene in Chinese patients with Dubin‑Johnson syndrome

Wu,Lina; Zhang,Wei; Jia,Siyu; Zhao,Xinyan; Zhou,Donghu; Xu,Anjian; Duan,Weijia; Wu,Zhen; Li,Hai; Zheng,Sujun; Nan,Yuemin; Jia,Jidong; Huang,Jian; Ou,Xiaojuan

doi:10.3892/etm.2018.6682

November-2018 Volume 16 Issue 5

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November-2018 Volume 16 Issue 5

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Article

Mutation analysis of the ABCC2 gene in Chinese patients with Dubin‑Johnson syndrome

Authors:
- Lina Wu
- Wei Zhang
- Siyu Jia
- Xinyan Zhao
- Donghu Zhou
- Anjian Xu
- Weijia Duan
- Zhen Wu
- Hai Li
- Sujun Zheng
- Yuemin Nan
- Jidong Jia
- Jian Huang
- Xiaojuan Ou
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Affiliations: Liver Research Center, Experimental Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China, Department of Hepatopancreatobiliary and Splenic Medicine, The Affiliated Hospital of Medical College of Chinese People's Armed Police Force, Tianjin 300192, P.R. China, Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China, Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
Pages: 4201-4206
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Published online on: September 3, 2018

https://doi.org/10.3892/etm.2018.6682
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Abstract

Dubin-Johnson syndrome (DJS) is a rare, autosomal recessive disorder characterized by predominantly conjugated hyperbilirubinemia, caused by a mutation in the adenosine triphosphate‑binding cassette subfamily C member 2 (ABCC2) gene coding the multidrug resistance‑associated protein 2 (MRP2) protein. ABCC2 mutations have been identified in patients with DJS worldwide; however, the mutation pattern of ABCC2 in China is not well studied. In the present study, the mutation pattern of the ABCC2 gene in Chinese patients with DJS was investigated. A total of 7 clinically confirmed patients with DJS were enrolled, and mutation analysis of the ABCC2 gene was performed by Sanger sequencing of genomic DNA extracted from whole blood. All 32 exons and the adjacent splice junction areas were sequenced. All cases were identified to harbor at least one non‑synonymous variant in the ABCC2 gene, including three known mutations in 3 cases and three novel variants (p.G693R, p.G808V and p.E647X) in the other 4 cases, with the known p.R393W and the novel p.G693R and p.E647X variants identified in 2 of the 7 cases (28.6%), respectively. All the identified mutations were heterozygous, and 1 case presented with a compound heterozygous mutation, namely p.G693R/p.G808V, while the other cases carried only one single mutation. The loss of membrane expression of MRP2 caused by the novel nonsense variant, p.E647X, was confirmed by immunohistochemical analysis of liver biopsy. The present study provided the first report on the mutation patterns of the ABCC2 gene in Chinese patients with DJS, and the clinical association of these mutations with the syndrome.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Mutation analysis of the ABCC2 gene in Chinese patients with Dubin‑Johnson syndrome

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