Fig. 1

Panel 1 Liver Histology. a Liver histology shows a cirrhotic aspect (HE, 4×). Giant multinucleated hepatocytes (arrows) and extramedullary erythropoietic foci are observed (star) (inset, HE, 10×). b In fibroedematous portal tracts dense inflammatory infiltration and biliary ducts proliferation (arrows) could be detected (HE, 20×). c Fibrous and edematous septa of micronodular cirrhosis (Masson trichromica, 4×). d Immunohistochemistry with anti-CK7 identifies dysmorphic neoduttules mimicking ductal plate malformation (arrows) (CK7, 20×). Panel 2 Mutations identified in ABCG5, ABCG8 and ZFYVE19 genes by WES and Sanger. a Upper panel: schematic structure of ABCG5 and ABCG8 transporters with mutations [ABCG5 p.Arg50Cys exon 2/13, c.148C > T (rs6756629) and ABCG8 p.Asp19His exon 1/13, c.55G > C (rs11887534)] indicated by a red star. Lower panel: results of Sanger sequencing of ABCG5 and ABCG8 mutations, non-synonymous mutations were homozygous in the patient and heterozygous in the two parents (grey boxes highlighting the amino acids influenced by these nucleotide mutations). b Upper panel: domain structure of ZFYVE19 protein showing the non-sense mutation [ZFYVE19, p.Arg223Ter exon 5/11, c.667C > T (rs375497733)] identified that introduces a premature stop codon leading to a 222 aa truncated protein compared to the 471 aa wild type one. Lower panel: results of Sanger sequencing of ZFYVE19 mutation; non-sense mutations were homozygous in the patient and heterozygous in the two parents (grey boxes highlighting the amino acids influenced by these nucleotide mutations). c Gas chromatography–mass spectrometry and flame ionization detector profile of sterols extract from patient's plasma