[Clinical and genetic analysis of cases of progressive familial intrahepatic cholestasis type 3].

Objective: To conduct clinical and genetic analysis in two cases of cholestatic liver disease to determine the specific etiology of cholestasis. Methods: Clinical data and the medical histories in family members of two cases were collected. The gene variation was detected by whole-exome sequencing technology. Sanger sequencing validation and bioinformatics analysis were performed on patients and their parents with suspected pathogenic mutations. Results: Whole-exome sequencing showed that the ABCB4 gene of case 1 (a male, 16 years old) had compound heterozygous mutations of c.646C > T from the father and c.927T > A from the mother, while the ABCB4 gene of case 2 (a female, 17 years old) had a compound heterozygous mutation of c.2784-1G > A from the father and c.646C > T from the mother. New mutation sites that had not been previously reported were c.646C > T, c.927T > A, and c.2784-1G > A. Conclusion: In this study, both cases had progressive familial intrahepatic cholestasis type 3 (PFIC-3) caused by ABCB4 gene mutations, and it also enriched the ABCB4 pathogenic variant spectrum. Whole-exome sequencing technology provides a reliable diagnostic tool for etiological analysis.