Volume 64, Issue 4, Pages 974-977 (April 2016) A de novo mutation in KCNN3 associated with autosomal dominant idiopathic non- cirrhotic portal hypertension  Bart G.P. Koot, Marielle Alders, Joanne Verheij, Ulrich Beuers, Jan M. Cobben  Journal of Hepatology  Volume 64, Issue 4, Pages 974-977 (April 2016) DOI: 10.1016/j.jhep.2015.11.027 Copyright © 2015 European Association for the Study of the Liver. Terms and Conditions

Fig. 1 Family pedigree. Journal of Hepatology 2016 64, 974-977DOI: (10.1016/j.jhep.2015.11.027) Copyright © 2015 European Association for the Study of the Liver. Terms and Conditions

Fig. 2 Liver histology of girl. (A) Sclerotic portal tract (arrow); PAS-amylase staining, 20×. (B) Portal tract with bile duct (∗), hepatic artery (#) and thickening of muscle wall ‘arterialisation’ of the portal vein (+); AZAN staining, 20×. Liver histology of father: (C) Portal tract with increased number of vessels, portal vein dilatation (∗) and paraportal shunting vessels (#); Elastica von Giesson staining, 10×. (D) Abnormal spacing of parenchymal venous structures (∗); Haematoxylin and Eosin staining, 4×. Journal of Hepatology 2016 64, 974-977DOI: (10.1016/j.jhep.2015.11.027) Copyright © 2015 European Association for the Study of the Liver. Terms and Conditions

Fig. 3 Sanger sequencing confirms the presence of the de novo mutation in KCNN3 in II-2 and transmission to his three affected children. Journal of Hepatology 2016 64, 974-977DOI: (10.1016/j.jhep.2015.11.027) Copyright © 2015 European Association for the Study of the Liver. Terms and Conditions

Fig. 4 Structure of the SK channel consisting of six transmembrane domains, a pore region (P) between S5 and S6, and calmodulin interacting with the channel’s intracellular COOH terminus. The mutation changes a conserved residue in the intracellular loop between the 4th and 5th transmembrane segment. Adapted from Ledoux et al. 2006 with permission. Journal of Hepatology 2016 64, 974-977DOI: (10.1016/j.jhep.2015.11.027) Copyright © 2015 European Association for the Study of the Liver. Terms and Conditions