PMC9024051_01
Computed tomography and magnetic resonance imaging of the proband. (A) Precontrast CT showed hyper-attenuation of liver parenchyma; (B) MRI T2-weighted image showed diffuse low signal intensity of liver parenchyma obviously.
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F1
Pre-contrast computed tomography (CT) revealed hepatomegaly with an increased attenuation over the liver and spleen, splenomegaly, and collateral circulation formation (Figure 1A). Magnetic resonance imaging (MRI) showed a typical decrease in T2-weighted signal intensity over the liver (Figure 1B). TFR2 gene. These mutations were further confirmed by Sanger sequencing (Supplementary Figure S1).
The liver histopathology of the proband [Panel (A, B), II-1] and the proband's sister [Panel (C, D), II-3]. (A) Increased collagen fibers stained green by Masson Trichrome stain in the expanded fibrous portal tract with cirrhosis (Masson trichrome, 100x); (B) Marked iron deposition in the hepatocytes and biliary epithelium (Prussian blue, 200x); (C) Marked deposition of hemosiderin in the hepatocytes (H&E, 100x); (D) The proband's sister had iron deposited in the periportal hepatocytes (Prussian blue, 200x).
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F2
The findings confirmed established cirrhosis with a marked deposition of iron in the hepatocytes and biliary epithelia, which is consistent with hemochromatosis (Figures 2A,B). Also, a fine needle aspiration biopsy was performed, which showed iron deposition in the periportal hepatocytes (Figures 2C,D). There is no electricity in the blank space in the model evaluation graph (Supplementary Figure S2), indicating that the model quality is acceptable.
3D structure of TFR2 protein. (A) wild-type; (B) mutant type c.G1288A (p.G430R); (C) partial mutation graph c.G1288A (p.G430R); (D) mutant type c.T960A (p.Y320X).
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F3
TFR2 protein in multiple species were studied (Supplementary Figure S3). The results showed that the two amino acids at positions 430 and 320 were absolutely conserved. As shown in Figure 3 , the secondary structure of the predicted mutation was not affected by the mutation c.1288G > A (p.G430R) but affected by the mutation c.960T > A (p.Y320X).
Family pedigree of patient. The parents of the proband should each had a heterozygous mutation (c.960T > A or c.G1288A). The proband's parents were not consanguineous.
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F4
TFR2 gene for his family members (Figure 4). The same heterozygous mutations were found in one of his sisters (II-3).