Mutations in the ATP8B1 gene cause two autosomal recessive disorders affecting liver: cholestasis, benign recurrent intrahepatic, 1 (BRIC1), cholestasis, progressive familial intrahepatic, 1 (PFIC1) and one autosomal dominant disorder: cholestasis, intrahepatic, of pregnancy, 1 (ICP1). BRIC2 is caused by mutations in the ABCB11 gene. PFIC can be caused by mutations in three other genes: ABCB11 (PFIC2), ABCB4 (PFIC3) and TJP2 (PFIC4).  Mutations in the ABCB4 gene have been reported in ICP3. BRIC is characterized by intermittent episodes of cholestasis without extrahepatic bile duct obstruction. PFIC is characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. ICP typically occurs in the third trimester and it recurs in 45 to 70% of subsequent pregnancies. Findings include pruritus, jaundice, increased serum bile salts, and abnormal liver enzymes. This condition is reversible, but it can result in fetal complications including premature labor, placental insufficiency and intrauterine death. Extrahepatic findings are not usually present in any of the conditions. However, a patient with clinical findings consistent with Alagille syndrome (ALGS, ATP8B1 related) was found to have compound heterozygous mutations in ATP8B1.

Copy number variation (CNV) analysis of the Cholestasis genes is also offered as a panel. Additionally, CTGT offers a comprehensive test (both NGS and CNV panels) for these genes. Panel genes are also offered as individual sequencing and deletion/duplication tests unless otherwise indicated.

The cholestasis NGS panel consists of four genes: ATP8B1, ABCB11, ABCB4 and TJP2.