Department of Hepatology, Fifth Medical Center, PLA General Hospital, No.100, West Fourth Ring Road, Fengtai District, Beijing, 100039, China.
Grandomics Biosciences, Beijing, 100098, China.
Orphanet J Rare Dis. 2024 Apr 12;19(1):157. doi: 10.1186/s13023-024-03179-w.
ABCB4 gene-related cholestatic liver diseases have a wide spectrum of clinical and genetic variations. The correlation between genotype and clinical phenotype still unclear. This study retrospectively analyzed the clinical and pathological characteristics of 23 patients with ABCB4 gene-related cholestatic liver diseases. Next-generation sequencing was used to identify the genetic causes.
The 23 included patients (15 children and 8 adults) were diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3), drug-induced liver injury (DILI), cirrhosis cholestasis, cirrhosis, and mild liver fibrosis. Nineteen patients underwent liver pathological examination of the liver, exhibiting fibrosis, small bile duct hyperplasia, CK7(+), Cu(+), bile duct deletion, and cirrhosis. Thirty ABCB4 variants were identified, including 18 novel variants.
ABCB4 gene-related cholestatic liver diseases have a wide spectrum of clinical and genetic variations. Biallelic ABCB4 mutation carriers tended to severe PFIC3, which mostly occurs in children; while ABCB4 non-biallelic variants can lead to milder ICP, LACP, DILI or overlapping, mostly in adults. Thus, the ABCB4 genotype has a specific correlation with the phenotype, but there are exceptions. Non-biallelic null mutations can cause severe diseases. The mechanisms underlying this genetic phenotype require further investigation.
ABCB4 基因相关胆汁淤积性肝病具有广泛的临床和遗传变异。基因型与临床表型之间的相关性尚不清楚。本研究回顾性分析了 23 例 ABCB4 基因相关胆汁淤积性肝病患者的临床和病理特征。采用下一代测序技术确定遗传原因。
23 例患者（15 例儿童和 8 例成人）被诊断为进行性家族性肝内胆汁淤积症 3 型（PFIC3）、药物性肝损伤（DILI）、胆汁淤积性肝硬化、肝硬化和轻度肝纤维化。19 例患者接受了肝脏病理检查，表现为纤维化、小胆管增生、CK7(+)、Cu(+)、胆管缺失和肝硬化。共发现 30 种 ABCB4 变异，包括 18 种新变异。
ABCB4 基因相关胆汁淤积性肝病具有广泛的临床和遗传变异。双等位基因 ABCB4 突变携带者倾向于严重的 PFIC3，主要发生在儿童；而 ABCB4 非双等位基因变异可导致较轻的 ICP、LACP、DILI 或重叠，主要发生在成人。因此，ABCB4 基因型与表型具有特定的相关性，但也存在例外。非双等位基因无效突变可导致严重疾病。这种遗传表型的机制需要进一步研究。
