Fig. 1.

Identification of a pathogenic variant in a large family with non-alcoholic fatty liver disease.

(A) Pedigree. Clinical features are described in Table 1. Diagnosis is indicated by shading: black, hepatocellular carcinoma; dark grey, cirrhosis; light grey, non-alcoholic steatohepatitis. Dashed lines indicate no investigations. ∗Exome sequenced. Blue letters indicate residue 564 in MTP. (B) Variant rs745447480 sequencing. (C) Local environment of I564 on MTP–PDI interface (hydrophobic pocket [white], polar [green], and charged [red/blue] residues). (D) 564T variant and common non-synonymous variants (side chains: C = cyan; O = red; N = blue) in a model derived from PDB ID:617S,⁸ a heterodimer of PDI (blue), and MTTP gene product (MTP) (grey). MTP, microsomal triglyceride transfer protein; PDI, protein disulfide isomerase.