In Family 2, an 18-year-old male (Patient 2) presented with intermittent mild jaundice for more than 9 years. This patient showed intermittent jaundice from the age of nine, which would be aggravated by fatigue. He had a previously free medical history and no special personal and family history (Figure 2A). When he came as a medical genetic outpatient to our hospital, he presented with yellow skin and sclera. In the physical examination, his liver could be palpated at the lower margin of the ribs. Patient 2's TBIL level was 110.6 mumol/L and his DBIL level was 70.4 mumol/L, with no other abnormalities in the liver function test. There were no abnormalities in autoimmune liver disease-associated antibodies or serum hepatitis B and C virus testing. A CT scan revealed hepatomegaly. The lower margin of the liver exceeded the lower costal margin (Table 1, Supplementary Figure S2). The WES indicated that Patient 2 harbored the heterozygous c.2980delA variant inherited from his mother and the heterozygous c.4465_4473delinsGGCCCACAG mutation inherited from his father (Figure 2B; Table 2). He was also diagnosed with DJS and chose to observe his jaundice (without drug interventions). In the telephone follow-up, he still complained of intermittent jaundice.
However, both patients refused the 99mTc-HIDA cholescintigraphy and liver biopsy. The candidate variants in the ABCC2 gene were validated by Sanger sequencing. The primer sequences are listed in Table A1. The methods of genetic testing are described in the supplementary materials. The family members participating in the study signed written informed consent forms. This study complied with the ethical guidelines of the Declaration of Helsinki and was approved by the ethics committee of the Second Xiangya Hospital of Central South University (2014 ethical approval No. S046).