Intrahepatic cholestasis of pregnancy in conjunction with a frameshift deletion in FGFR4.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by increased serum bile acid levels in the third trimester of pregnancy and resolves quickly after delivery. Here, we present the case of a 29-year-old woman who developed idiopathic liver damage during puberty, and subsequently ICP and severe pruritus during two pregnancies. DNA sequencing revealed a heterozygous deletion (c.393_delG) in the fibroblast growth factor receptor 4 (FGRF4) gene causing a premature stop codon. The resulting FGFR4 haploinsufficiency is likely to impede the enterohepatic feedback repression of hepatic bile acid synthesis via FXR and FGF19. It represents a new genetic etiology of ICP.