Abstract
Background
Heterozygous ABCB4 variants are not routinely tested in adults with cholestasis because of their supposed
rarity and high costs.
Methods
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.
Results
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.
Conclusions
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.
Keywords
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Article info
Publication history
Published online: December 31, 2020
Accepted:
December 5,
2020
Received:
October 28,
2020
Footnotes
Financial support: none.
Identification
Copyright
© 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
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- ABCB4-alteration screening in adult-onset cholestasisDigestive and Liver DiseaseVol. 53Issue 3
- PreviewOver 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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