In Family 1, a 29-year-old woman (Patient 1) was born to nonconsanguineous parents although her grandparents were cousins (Figure 1A). She was affected with low-grade predominantly conjugated hyperbilirubinemia for more than 6 years. This patient was tested for hyperbilirubinemia in a health physical examination in 2015. There were no other significant abnormalities in her liver function test. She received no other medical treatment then. During her pregnancy, her jaundice was markedly aggravated. She gave birth on 18 August 2018. The obstetrician used reduced glutathione (1.2 g/d, from 16 August 2018 to 20 August 2018) and ursodeoxycholic acid (500 mg/d, from 20 August 2018 to 31 August 2018) to control her jaundice. Her clinical jaundice gradually disappeared after childbirth in 2018. She took oral contraceptives from January 2021 and presented with recurrent mild jaundice again. The jaundice was in remission after she stopped taking oral contraceptives; she was never affected with pruritus. The patient had a previously free medical history. When she came to us as a medical genetic outpatient in July 2021, the physical examination revealed mild splenomegaly. The timeline with relevant data for Patient 1 is shown in Supplementary Figure S1. During the patient's pregnancy, her level of total bilirubin (TBIL) ranged from 43.1 mumol/L to 82.8 mumol/L (normal range: 3.4-17.1 mumol/L). Her direct bilirubin (DBIL) level ranged from 25.2 mumol/L to 65.1 mumol/L (normal range: 0-6 mumol/L). The ratio of DBIL/TBIL was always greater than 50%. There were no abnormalities in other liver function indexes. She was serologically negative for hepatitis A, B, C, and E viruses. There were no abnormalities in coagulation function, autoimmune liver disease-associated antibodies, immunoglobulin G, or serum ceruloplasmin testing. The abdominal ultrasound examination revealed her portal vein diameter to be about 10 mm and the portal venous maximum velocity was 18 cm/s. The thickness of her spleen was about 49 mm and its inferior margin was about 20 mm below the costal margin. A hepatic hemangioma was also detected by the ultrasound examination (Supplementary Figure S2; Table 1). The whole-exome sequencing (WES) was conducted in July 2021, revealing that Patient 1 carried both the heterozygous c.2980delA and c.1834C>T ABCC2 mutations. Her son also shared the heterozygous c.1834C>T ABCC2 mutation (Figure 1B; Table 2). Considering her symptoms, clinical examinations, and genetic testing, she was diagnosed with DJS. Intrahepatic cholestasis of pregnancy (ICP) was excluded.