# A Rare Nonsense Mutation in the ABCB4 Gene Associated with Progressive Familial Intrahepatic Cholestasis Type 3: A Case Report

## TL;DR

A rare ABCB4 gene mutation causing progressive liver disease in a young woman is reported, highlighting the importance of genetic testing for accurate diagnosis and treatment.

## Contribution

A novel ABCB4 gene variant (c.2757T > A) is identified as a cause of PFIC3 in a young patient with no prior liver disease history.

## Key findings

- A likely pathogenic ABCB4 gene variant (c.2757T > A) was detected in a young woman with PFIC3.
- Liver cirrhosis and splenomegaly were confirmed via imaging and histological analysis.
- Ursodeoxycholic acid therapy led to moderate improvement in liver function tests.

## Abstract

Background: Progressive familial intrahepatic cholestasis (PFIC) describes a group of genetically heterogeneous disorders. Several mutations in the ATP-Binding Cassette Subfamily B Member 4 (ABCB4) gene have been confirmed to cause reduced phosphatidylcholine levels in bile, leading to a deficiency of biliary vesicles and instability of mixed in micelles. The disease spectrum ranges from PFIC type 3 (PFIC3) to milder conditions. Herein, we present a rare case of PFIC3 in a young woman, emphasizing the importance of early detection and management. Methods: The patient was diagnosed using next-generation sequencing, with genetic testing and analysis performed by the Chengdu Hua Chuang Testing Institute. Variant pathogenicity was evaluated according to the American College of Medical Genetics and Genomics guidelines and classified into five categories: pathogenic, likely pathogenic, uncertain significance, likely benign, and benign. Nomenclature was assigned following the Human Genome Variation Society standards. Results: Contrast-enhanced abdominal computed tomography demonstrated liver cirrhosis with marked splenomegaly. Histological examination of liver biopsy specimens using hematoxylin and eosin and Masson staining further confirmed cirrhotic changes. Genetic testing was subsequently performed and revealed a likely pathogenic variant, c.2757T > A (p. Tyr919Ter), in exon 22 of the ABCB4 gene, which was also detected in the patient’s mother but absent in her father. Finally, PFIC3 was diagnosed. Following initiation of ursodeoxycholic acid therapy, the patient showed moderate improvement in liver function tests, underscoring a clinical case with therapeutic implications. Conclusions: Molecular genetic analyses of ABCB4 are essential for the accurate diagnosis of PFIC3. Clinicians should consider cholestatic liver diseases, particularly PFIC, as a differential diagnosis in cases of liver cirrhosis with unknown etiology, especially in young patients who lack prior symptoms or a family history of liver disease.