Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency
Journal
JHEP reports : innovation in hepatology
Journal Volume
5
Journal Issue
2
Date Issued
2023-02
Author(s)
Felzen, Antonia
van Wessel, Daan B E
Gonzales, Emmanuel
Thompson, Richard J
Jankowska, Irena
Shneider, Benjamin L
Sokal, Etienne
Grammatikopoulos, Tassos
Kadaristiana, Agustina
Jacquemin, Emmanuel
Spraul, Anne
Lipiński, Patryk
Czubkowski, Piotr
Rock, Nathalie
Shagrani, Mohammad
Broering, Dieter
Nicastro, Emanuele
Kelly, Deirdre
Nebbia, Gabriella
Arnell, Henrik
Fischler, Björn
Hulscher, Jan B F
Serranti, Daniele
Arikan, Cigdem
Polat, Esra
Debray, Dominique
Lacaille, Florence
Goncalves, Cristina
Hierro, Loreto
Muñoz Bartolo, Gema
Mozer-Glassberg, Yael
Azaz, Amer
Brecelj, Jernej
Dezsőfi, Antal
Calvo, Pier Luigi
Grabhorn, Enke
Hartleif, Steffen
van der Woerd, Wendy J
Kamath, Binita M
Wang, Jian-She
Li, Liting
Durmaz, Özlem
Kerkar, Nanda
Jørgensen, Marianne Hørby
Fischer, Ryan
Jimenez-Rivera, Carolina
Alam, Seema
Cananzi, Mara
Laverdure, Noemie
Ferreira, Cristina Targa
Guerrero, Felipe Ordoñez
Wang, Heng
Sency, Valerie
Kim, Kyung Mo
de Carvalho, Elisa
Fabre, Alexandre
Bernabeu, Jesus Quintero
Zellos, Aglaia
Alonso, Estella M
Sokol, Ronald J
Suchy, Frederick J
Loomes, Kathleen M
McKiernan, Patrick J
Rosenthal, Philip
Turmelle, Yumirle
Horslen, Simon
Schwarz, Kathleen
Bezerra, Jorge A
Wang, Kasper
Hansen, Bettina E
Verkade, Henkjan J
Abstract
Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship.
Subjects
ABCB11, ATP-binding cassette, sub-family B member 11; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BSEP; BSEP, bile salt export pump; ChiLDReN, Childhood Liver Disease Research Network; GGT, gamma-glutamyltransferase; HCC, hepatocellular carcinoma; LTx, liver transplantation; NAPPED, NAtural course and Prognosis of PFIC and Effect of biliary Diversion; NLS, native liver survival; PFIC2; PFIC2, progressive familial intrahepatic cholestasis type 2; PPTM, predicted protein truncating mutation; REDCap, Research Electronic Data Capture; TSB, total serum bilirubin; UDCA, ursodeoxycholic acid; compound heterozygosity; genotype; interruption of the enterohepatic circulation; phenotype; sBAs, serum bile acids; siEHC, surgical interruption of the enterohepatic circulation
SDGs
Publisher
ELSEVIER
Type
journal article