PMC9808042_01
(A) MRI showed multiple microscopic cysts in the medulla of the patient's kidney. (B,C) Interstitial edema and tubular destruction (PAS 400x). (D) Transmission electron micrograph of tubular epithelial cytoplasm showed mitochondrial swelling, focal cristae damage, and vacuolation (arrows). (E) The IgG4 staining in the interstitium. (F) Uromodulin was expressed in the cytoplasm of most cells of the thick ascending limb of Henle. Some epithelial cells were negative or weakly/partial UMOD positive along the luminal side (arrows). No UMOD protein accumulation was observed (400x).
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F1
However, magnetic resonance imaging (MRI) of the kidneys revealed some occasional cysts at the corticomedullary boundary (Figure 1A). Electron microscopy showed mitochondrial swelling, focal cristae damage, and vacuolation of tubular cells (Figures 1B-D). Glomerulonephritis, IgG4-related disease, and alport syndrome were ruled out (Figure 1E). However, abnormal UMOD accumulations, typically as polymorphic unstructured materials by PAS staining, were not noteworthy (Figure 1F).
(A) The patient carried a heterozygous mutation in the UMOD gene c.280T > C (p.C94R), and neither of her parents carried this mutation. (B) Different interaction patterns in wild type and p.C94R mutant. The left one is for the wild-type structure and the right one is for the p.C94R mutant. The electrostatic surface is colored according to a scale from red (negative, min = -5.0 kT/e) to blue (positively, max = 5.0 kT/e). The backbone structure is shown in cartoon representation, Cys94, Cys106, and Ser78 as sticks with the rest of the side chains as lines. The distance between the hydrogen donor and the hydrogen acceptor is marked in the unit of Angstrom (A).
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F2
A de novo heterozygous mutation c.280T > C (p.Cys94Arg) in the UMOD gene was found, which was absent in her parents (Figure 2A). In addition, the mutant arginine was more hydrophilic, which might prefer protein surface to the interior and result in protein misfolding (Figure 2B).