Year 2019 / Volume 111 / Number 1
Case Report
Expanding the mutational spectrum of the ABCB4 gene in inherited adult cholestatic liver disorders with four novel pathogenic variants

76-79

DOI: 10.17235/reed.2018.5828/2018

Minh-Tuan Huynh, Jean-Louis Delaunay, Laure Muller, Christophe Corpechot, Cong Toai Tran, Véronique Barbu,

Abstract
Low phospholipid-associated cholelithiasis and intrahepatic cholestasis of pregnancy are two MDR3-related inherited liver disorders caused by biallelic or monoallelic ABCB4 loss-of-function variants. Low phospholipid-associated cholelithiasis is clinically characterized by the early onset of symptomatic cholelithiasis in young adults while intrahepatic cholestasis of pregnancy is a distinct clinical entity associated with adverse fetal outcomes. Of note, patients carrying ABCB4 sequence variations commonly exhibit phenotypic expression over a wide continuum due to environmental and hormonal contributing factors and genetic modifiers. Patients with an early diagnosis of MDR3-related diseases could benefit from ursodeoxycholic acid treatment in order to prevent acute and chronic complications as well as adverse pregnancy outcomes. We herein report five patients with an overlapping phenotype from low phospholipid-associated cholelithiasis to intrahepatic cholestasis of pregnancy, harboring five ABCB4 missense variants, four of which were novel. Our study highlights the phenotypic and genetic heterogeneity of inherited cholestatic liver diseases and also expands the mutation spectrum of ABCB4 sequence variations in adult cholestatic liver diseases.
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References
1. Poupon R, Rosmorduc O, Boëlle PY, et al. Genotype-phenotype relationships in the low phospholipid-associated cholelithiasis syndrome: a study of 156 consecutive patients. Hepatology 2013; 58: 1105-1110.
2. Rosmorduc O, Poupon R. Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene. Orphanet J Rare Dis 2007; 2: 29.
3. Dixon PH, Sambrotta M, Chambers J, et al. An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy. Sci Rep 2017; 7: 11823.
4. Dixon PH, Wadsworth CA, Chambers J, et al. A comprehensive analysis of common genetic variation around six candidate loci for intrahepatic cholestasis of pregnancy. Am J Gastroenterol 2014; 109: 76-84.
5. Buch S, Schafmayer C, Völzke H, et al. A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nat Genet 2007; 39: 995-999.
6. Von Kampen O, Buch S, Nothnagel M, et al. Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus. Hepatology 2013; 57: 2407-2417.
7. Poupon R, Arrive L, Rosmorduc O. The cholangiographic features of severe forms of ABCB4/MDR3 deficiency-associated cholangiopathy in adults. Gastroenterol Clin Biol 2010; 34: 380-387.
8. Van der Woerd WL, van Mil S W, Stapelbroek JM, et al. Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy. Best Pract Res Clin Gastroenterol 2010; 24: 541-553.
9. Johnston RC, Stephenson ML, Nageotte MP. Novel heterozygous ABCB4 gene mutation causing recurrent first-trimester intrahepatic cholestasis of pregnancy. J Perinatol 2014; 34: 711-712.
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Huynh M, Delaunay J, Muller L, Corpechot C, Tran C, Barbu V, et all. Expanding the mutational spectrum of the ABCB4 gene in inherited adult cholestatic liver disorders with four novel pathogenic variants. 5828/2018


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Publication history

Received: 14/07/2018

Accepted: 30/09/2018

Online First: 19/11/2018

Published: 17/01/2019

Article revision time: 67 days

Article Online First time: 128 days

Article editing time: 187 days


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