학술논문
Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency
Document Type
article
Author
Antonia Felzen; Daan B.E. van Wessel; Emmanuel Gonzales; Richard J. Thompson; Irena Jankowska; Benjamin L. Shneider; Etienne Sokal; Tassos Grammatikopoulos; Agustina Kadaristiana; Emmanuel Jacquemin; Anne Spraul; Patryk Lipiński; Piotr Czubkowski; Nathalie Rock; Mohammad Shagrani; Dieter Broering; Emanuele Nicastro; Deirdre Kelly; Gabriella Nebbia; Henrik Arnell; Björn Fischler; Jan B.F. Hulscher; Daniele Serranti; Cigdem Arikan; Esra Polat; Dominique Debray; Florence Lacaille; Cristina Goncalves; Loreto Hierro; Gema Muñoz Bartolo; Yael Mozer-Glassberg; Amer Azaz; Jernej Brecelj; Antal Dezsőfi; Pier Luigi Calvo; Enke Grabhorn; Steffen Hartleif; Wendy J. van der Woerd; Binita M. Kamath; Jian-She Wang; Liting Li; Özlem Durmaz; Nanda Kerkar; Marianne Hørby Jørgensen; Ryan Fischer; Carolina Jimenez-Rivera; Seema Alam; Mara Cananzi; Noemie Laverdure; Cristina Targa Ferreira; Felipe Ordoñez Guerrero; Heng Wang; Valerie Sency; Kyung Mo Kim; Huey-Ling Chen; Elisa de Carvalho; Alexandre Fabre; Jesus Quintero Bernabeu; Aglaia Zellos; Estella M. Alonso; Ronald J. Sokol; Frederick J. Suchy; Kathleen M. Loomes; Patrick J. McKiernan; Philip Rosenthal; Yumirle Turmelle; Simon Horslen; Kathleen Schwarz; Jorge A. Bezerra; Kasper Wang; Bettina E. Hansen; Henkjan J. Verkade
Source
JHEP Reports, Vol 5, Iss 2, Pp 100626- (2023)
Subject
Language
English
ISSN
2589-5559
Abstract
Background & Aims: 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. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p