Abstract
Progressive familial intrahepatic cholestasis (PFIC) includes a group of genetic autosomal recessive disorders that predominantly affects young children and results in early-onset progressive liver damage. Variations in ABCB4 have been shown to cause PFIC3. However, the association between ABCB4 genotype and clinical manifestations remains unclear. We investigated the clinical manifestations and genetic features of a Chinese Han pedigree with PFIC3. A 15-year-old boy, with high-serum gamma-glutamyl transferase (γ-GT) cholestatic cirrhosis, was diagnosed with PIFC3. After ursodeoxycholic acid (UDCA) treatment, the boy stayed in a relatively stable state with mild itching, and elevated γ-GT exhibited a remarkable decrease. Genetic testing identified a novel compound heterozygous mutation L842P/V1051A in ABCB4, which was inherited from his mother and father, respectively. Several predictive software suggested that these two mutations are pathogenic. Interestingly, the same compound heterozygous mutation was also found in his two sisters, one of whom had a history of intrahepatic cholestasis of pregnancy (ICP) and the other had asymptomatic gallstones. Therefore, this novel compound heterozygous mutation L842P/V1051A caused a continuum of ABCB4-related diseases including ICP, cholelithiasis and PFIC3 in our pedigree. The inconsistency between genotypes and phenotypes may be influenced by other factors. Genetic testing will be useful for diagnosis and genetic counseling.