Clinical and molecular genetic characteristics of pediatric PFIC3 patients: three novel variants and prognosis for parental liver transplantation
Abstract Progressive Familial Intrahepatic Cholestasis Type 3 (PFIC3) is a rare inherited liver disease caused by a mutation in the ABCB4 gene, leading to dysfunction of multidrug resistance protein 3 (MDR3). The earlier the onset of PFIC3 in children is, the more severe the prognosis. The diagnosis...
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BMC
2025-04-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03670-y |
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| author | Jiqiang Hu Chenyu Yang Bingqian Tan Qiang Xiong Ying Le Jianyang Hu Haoming Wang Xiaoke Dai Mingman Zhang |
| author_facet | Jiqiang Hu Chenyu Yang Bingqian Tan Qiang Xiong Ying Le Jianyang Hu Haoming Wang Xiaoke Dai Mingman Zhang |
| author_sort | Jiqiang Hu |
| collection | DOAJ |
| description | Abstract Progressive Familial Intrahepatic Cholestasis Type 3 (PFIC3) is a rare inherited liver disease caused by a mutation in the ABCB4 gene, leading to dysfunction of multidrug resistance protein 3 (MDR3). The earlier the onset of PFIC3 in children is, the more severe the prognosis. The diagnosis of PFIC3 is typically based on clinical symptoms, laboratory tests, and imaging assessments, with final confirmation requiring genetic testing. The aim of this study was to investigate the associations between genetic mutations in PFIC3 and clinical features, molecular genetics, and liver histopathology to improve early recognition and understanding of this disease. By analysing the data of three children with PFIC3 who underwent parental liver transplantation, we were able to gain a deeper understanding of the complexity and diversity of the disease. With respect to molecular genetics, we identified five mutation sites in the ABCB4 gene, including three newly discovered mutations. Immunohistochemical analysis revealed reduced expression of the MDR3 protein in child 1 and no expression in child 2 or child 3, revealing an intrinsic link between the ABCB4 gene and the MDR3 protein. Histopathologically, all three patients presented with significant portal vein fibrosis or cholestatic liver cirrhosis. In conclusion, this study emphasizes the importance of molecular genetic and pathological evaluation of patients with PFIC3 mutations and elucidates the impact of these three mutations on the course of the disease in children, for whom early symptomatic treatment and early preparation for liver transplantation are options worth considering. |
| format | Article |
| id | doaj-art-1c56c3fe6ceb4ef1bfee2e5bacd7c52a |
| institution | OA Journals |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-1c56c3fe6ceb4ef1bfee2e5bacd7c52a2025-08-20T02:17:10ZengBMCOrphanet Journal of Rare Diseases1750-11722025-04-0120111110.1186/s13023-025-03670-yClinical and molecular genetic characteristics of pediatric PFIC3 patients: three novel variants and prognosis for parental liver transplantationJiqiang Hu0Chenyu Yang1Bingqian Tan2Qiang Xiong3Ying Le4Jianyang Hu5Haoming Wang6Xiaoke Dai7Mingman Zhang8Department of Pediatric Hepatobiliary Surgery National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children’S Hospital of Chongqing Medical UniversityDepartment of Pediatric Hepatobiliary Surgery National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children’S Hospital of Chongqing Medical UniversityDepartment of Pediatric Hepatobiliary Surgery National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children’S Hospital of Chongqing Medical UniversityDepartment of Pediatric Hepatobiliary Surgery National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children’S Hospital of Chongqing Medical UniversityDepartment of Pediatric Hepatobiliary Surgery National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children’S Hospital of Chongqing Medical UniversityDepartment of Pediatric Hepatobiliary Surgery National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children’S Hospital of Chongqing Medical UniversityDepartment of Pediatric Hepatobiliary Surgery National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children’S Hospital of Chongqing Medical UniversityDepartment of Pediatric Hepatobiliary Surgery National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children’S Hospital of Chongqing Medical UniversityDepartment of Pediatric Hepatobiliary Surgery National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children’S Hospital of Chongqing Medical UniversityAbstract Progressive Familial Intrahepatic Cholestasis Type 3 (PFIC3) is a rare inherited liver disease caused by a mutation in the ABCB4 gene, leading to dysfunction of multidrug resistance protein 3 (MDR3). The earlier the onset of PFIC3 in children is, the more severe the prognosis. The diagnosis of PFIC3 is typically based on clinical symptoms, laboratory tests, and imaging assessments, with final confirmation requiring genetic testing. The aim of this study was to investigate the associations between genetic mutations in PFIC3 and clinical features, molecular genetics, and liver histopathology to improve early recognition and understanding of this disease. By analysing the data of three children with PFIC3 who underwent parental liver transplantation, we were able to gain a deeper understanding of the complexity and diversity of the disease. With respect to molecular genetics, we identified five mutation sites in the ABCB4 gene, including three newly discovered mutations. Immunohistochemical analysis revealed reduced expression of the MDR3 protein in child 1 and no expression in child 2 or child 3, revealing an intrinsic link between the ABCB4 gene and the MDR3 protein. Histopathologically, all three patients presented with significant portal vein fibrosis or cholestatic liver cirrhosis. In conclusion, this study emphasizes the importance of molecular genetic and pathological evaluation of patients with PFIC3 mutations and elucidates the impact of these three mutations on the course of the disease in children, for whom early symptomatic treatment and early preparation for liver transplantation are options worth considering.https://doi.org/10.1186/s13023-025-03670-yProgressive familial intrahepatic cholestasis type 3ABCB4MDR3Cholestasis |
| spellingShingle | Jiqiang Hu Chenyu Yang Bingqian Tan Qiang Xiong Ying Le Jianyang Hu Haoming Wang Xiaoke Dai Mingman Zhang Clinical and molecular genetic characteristics of pediatric PFIC3 patients: three novel variants and prognosis for parental liver transplantation Orphanet Journal of Rare Diseases Progressive familial intrahepatic cholestasis type 3 ABCB4 MDR3 Cholestasis |
| title | Clinical and molecular genetic characteristics of pediatric PFIC3 patients: three novel variants and prognosis for parental liver transplantation |
| title_full | Clinical and molecular genetic characteristics of pediatric PFIC3 patients: three novel variants and prognosis for parental liver transplantation |
| title_fullStr | Clinical and molecular genetic characteristics of pediatric PFIC3 patients: three novel variants and prognosis for parental liver transplantation |
| title_full_unstemmed | Clinical and molecular genetic characteristics of pediatric PFIC3 patients: three novel variants and prognosis for parental liver transplantation |
| title_short | Clinical and molecular genetic characteristics of pediatric PFIC3 patients: three novel variants and prognosis for parental liver transplantation |
| title_sort | clinical and molecular genetic characteristics of pediatric pfic3 patients three novel variants and prognosis for parental liver transplantation |
| topic | Progressive familial intrahepatic cholestasis type 3 ABCB4 MDR3 Cholestasis |
| url | https://doi.org/10.1186/s13023-025-03670-y |
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