Progressive familial intrahepatic cholestasis (PFIC)refers to a heterogeneous group of autosomal recessive liver disorders of children characterized by defects in the transporters of conjugated bile acids into the bile canaliculus.The third type of PFIC (PFIC3) caused by defects in the ABCB4 gene usually has an elevated serum gamma-glutamyltransferase (GGT)activity.Here, we sequenced the whole exome of two siblings with PFIC3 phenotype and identified a homozygous mutation c.2176C-T transition (p.P726L) in exon 17 of ABCB4.Sanger sequencing further confirmed that the mutant alleles were inherited from their nonconsanguineous parents.The fact that the parents were both Chinese ethnic minorities suggests the importance of investigating the distribution of rare variants in specific groups.Our findings demonstrate that exome sequencing is a useful means of mapping monogenic disease mutation.We also propose the approach to be applied to genetic counseling and prenatal diagnosis.