ABCB4 mutations in adult patients with cholestatic liver disease: impact and phenotypic expression

  title={ABCB4 mutations in adult patients with cholestatic liver disease: impact and phenotypic expression},
  author={Dario Degiorgio and Andrea Crosignani and Carla Colombo and Domenico Bordo and Massimo Zuin and Emanuela Vassallo and Marie Lousie Syr{\'e}n and Domenico A Coviello and Pier Maria Battezzati},
  journal={Journal of Gastroenterology},
BackgroundThe ABCB4 gene encodes the MDR3 protein. Mutations of this gene cause progressive familial intrahepatic cholestasis type 3 (PFIC3) in children, but their clinical relevance in adults remains ill defined. The study of a well-characterized adult patient series may contribute to refining the genetic data regarding cholangiopathies of unknown origin. Our aim was to evaluate the impact of ABCB4 mutations on clinical expression of cholestasis in adult patients.MethodsWe consecutively… 
Common ABCB4 and ABCB11 genotypes are associated with idiopathic chronic cholestasis in adults.
The common ABCB4 c.711A>T and ABCB11 p.A444V polymorphisms are more prevalent in adult patients with idiopathic cholestasis than in healthy controls and may therefore represent risk factors for the development of chronic cholESTatic liver disease.
ABCB4 variants in adult patients with cholestatic disease are frequent and underdiagnosed.
Clinical phenotype of adult-onset liver disease in patients with variants in ABCB4, ABCB11, and ATP8B1.
Variants in ATP8B1, ABCB11, and ABCB4 underlie the most prevalent forms of progressive familial intrahepatic cholestasis, and they should no longer be considered recessive Mendelian traits.
Infantile cholestasis related to ABCB4 gene mutation and cytomegalovirus (CMV) infection: a case report
It was considered that patient with heterozygous ABCB4 gene mutation had residual gene expression and a relatively low level of MDR3 proteins, but CMV infection further down regulated the gene expression, disturbing the bile secretion, leading to cholestasis.
The wide phenotypic and genetic spectrum of ABCB4 gene deficiency: A case series.
  • D. Falcão, I. Pedroto, T. Moreira
  • Medicine, Biology
    Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
  • 2021
Familial intrahepatic cholestasis: New and wide perspectives.
ABCB4 disease: Many faces of one gene deficiency.
ABCB4 Gene Aberrations in Human Liver Disease: An Evolving Spectrum.
Current functional classifications for ABCB4 deficiency-associated mutations can guide the development of novel genotype-based targeted pharmacotherapies for these conditions.
A novel compound heterozygous mutation in ABCB4 gene in a pedigree with progressive familial intrahepatic cholestasis 3: a case report.
A novel compound heterozygous mutation L842P/V1051A caused a continuum of ABCB4-related diseases including ICP, cholelithiasis and PFIC3 in the authors' pedigree and will be useful for diagnosis and genetic counseling.


The spectrum of liver diseases related to ABCB4 gene mutations: pathophysiology and clinical aspects.
There is evidence that a biallelic or monoallelic ABCB4 defect causes or predisposes to several human liver diseases (PFIC3, low phospholipid associated cholelithiasis syndrome, intrahepatic cholestasis of pregnancy, drug-induced liver injury, transient neonatal cholESTasis, adult biliary fibrosis, or cirrhosis).
Clinical Features and Genotype-Phenotype Correlations in Children With Progressive Familial Intrahepatic Cholestasis Type 3 Related to ABCB4 Mutations
Disease-causing mutations on both alleles were found to be associated with reduced liver expression of ABCB4 protein, lack of response to ursodeoxycholic acid therapy, and progression to cirrhosis and end-stage liver disease, whereas mild genotypes were generally associated with less severe disease and, often, absence of symptoms.
A mutation in the canalicular phospholipid transporter gene, ABCB4, is associated with cholestasis, ductopenia, and cirrhosis in adults
It is shown that a missense mutation in ABCB4 is a cause for ductopenic CLD in adulthood and should be generally considered in all patients with cholestatic liver disease of unknown etiology regardless of age and onset of disease.
Functional analysis of ABCB4 mutations relates clinical outcomes of progressive familial intrahepatic cholestasis type 3 to the degree of MDR3 floppase activity
Experimental evidence is provided of the correlation between the degree of MDR3 floppase activity and the clinical outcomes of PFIC3, and of the impact of ABCB4 mutations on these outcomes.
ABCB4 heterozygous gene mutations associated with fibrosing cholestatic liver disease in adults.
Heterozygous ABCB4 mutations were detected in 34% of adults with unexplained cholestasis, for the most part without biliary symptoms, and could result in significant liver fibrosis.
Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3)
The results of this study provide evidence of the broad allelic heterogeneity of the disease, with causative mutations spread along 14 of the 27 coding exons but with higher prevalence on exon 17 that could contain an evolutionary marker for mammalian ABCB4 genes in the seventh transmembrane segment.
ABCB4 deficiency: A family saga of early onset cholelithiasis, sclerosing cholangitis and cirrhosis and a novel mutation in the ABCB4 gene
  • G. Denk, H. Bikker, T. Pusl
  • Medicine
    Hepatology research : the official journal of the Japan Society of Hepatology
  • 2010
A family with ABCB 4 deficiency and LPAC syndrome associated with a novel mutation (c.3203T>A) in the ABCB4 gene is reported on.
A multidrug resistance 3 gene mutation causing cholelithiasis, cholestasis of pregnancy, and adulthood biliary cirrhosis.
The present case, which accumulates the 3 clinical disorders assocaited with MDR3 deficiency, shows that this condition should be suspected not only in children or young people with high gamma-glutamyl transpeptidase cholestasis but also in middle-aged or older patients with chronic idiopathic cholESTasis, especially when there is a previous history of cholmostasis of pregnancy or juvenile cholelithiasis.
The genetics of complex cholestatic disorders.
A lithogenic variant in the gene that encodes the hepatobiliary transporter ABCG8 has been identified as a risk factor for gallstone disease and this variant has been associated with altered cholesterol excretion and metabolism.