Liver, Pancreas and Biliary Tract| Volume 53, ISSUE 3, P329-344, March 2021

ABCB4 variants in adult patients with cholestatic disease are frequent and underdiagnosed

Published:December 31, 2020DOI:



      Heterozygous ABCB4 variants are not routinely tested in adults with cholestasis because of their supposed rarity and high costs.


      Nineteen adult patients presenting with unexplained cholestasis, and/or recurrent gallstones were included; genotyping was not done in five due to lack of health insurance approval.


      heterozygous ABCB4 variants were identified in seven patients, followed by cascade testing of 12 family members: one patient underwent liver transplantation at age 40 for end-stage liver disease; one had compensated cirrhosis; all symptomatic adults had gallstones, including four with low phospholipid-associated cholelithiasis; four had intrahepatic cholestasis of pregnancy; all children and one 54-year old female were asymptomatic. Genotype: Families A and C: c.2211G>A (p.Ala737=) combined with c.959C>T (p.Ser320Phe) in one subject; Family B: c.1130T>C (p.Ile377Thr); Family D: large deletion removing ABCB4 exons 1-4 plus ABCB1, RUNDC3B, SLC25A40, DBF4, ADAM22 exons 1-3; Family E: c.1565T>C (p.Phe522Ser) ; Family F: c.1356+2T>C combined with c.217C>G (p.Leu73Val). All patients responded to ursodeoxycholic acid.


      We found ABCB4 variants in half of the adults with unexplained cholestasis and/or recurrent gallstones presenting at our center, suggesting that this condition is underdiagnosed and undertreated, with serious consequences not only for the patients and their families, but also in terms of healthcare costs.


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        Digestive and Liver DiseaseVol. 53Issue 3
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          Over the last decade, modern genetic studies have provided major insights into the pathophysiology of chronic biliary diseases. Novel computational methods such as genome-wide association studies (GWAS), next-generation sequencing (NGS), and whole-genome sequencing (WGS) have played an important role in identifying possible connections between single nucleotide polymorphisms (SNPs) and various biliary and liver disorders [1]. However, these methods have not assigned specific genetic variants to the corresponding clinical phenotypes.
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