PMC10102471_01
Pedigree of the family affected. The arrow identifies the proband. The crossed symbol indicates the deceased individual.
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F1
The proband (II-2 in Figure 1) was a 12-year-old boy diagnosed with AS coexisting with WD at the age of 11 years. The visual and auditory functions, hepatic and renal functions, and urinalysis of the patient's parents (I-1, I-2 in Figure 1) and younger brother (II-3 in Figure 1) were normal.
Histopathologic lesions. (A) H&E stain (x200) showing glomeruli mesangial hypercellularity, a thickened mesangial matrix, and a ring-like mixed crescent form ( ); (B) the renal tubules depicting interstitial inflammatory cell infiltration and interstitial fibrosis ( ) by a light microscopy study (H&E stain, x200); (C) immunofluorescence staining showing granular deposition of IgM (++) within the mesangium; and (D) electron micrograph showing abnormal glomerular capillary basement membrane thickness, uneven thickness, (ranging from 350 to 900 nm), layered ( ), focal torn, and endothelial cell insertion.
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F2
An analysis of renal biopsy specimens using light microscopy showed the formation of annular cellular and fibrous crescents in three glomeruli (3/16 glomerulus) (Figure 2A), hypertrophy of other glomeruli, increased number of intrinsic cells, lobulation of glomeruli with mesangial hypercellularity, segmental thickening of the mesangial matrix and a small amount of redophilic deposits in the mesangial area, vacuolated renal tubular epithelial cells and the presence of casts in the tubular lumen, interstitial focal inflammatory cell infiltration, interstitial fibrosis, and mild edema (Figure 2B). Immunofluorescence staining of kidney tissue revealed granular deposition of IgM (++) within the mesangium (Figure 2C) and showed negativity for IgG, IgA, C3, C4, C1q, and Fibri. Electron microscopy also revealed an abnormal glomerular capillary basement membrane thickness, which was uneven (ranging from 350 to 900 nm) or layered, focal torn, and endothelial cell insertion; and multiple lysosomes in the podocyte cytoplasm, with widely fused foot processes (Figure 2D).
(A) Partial DNA sequences in the COL4A5 gene of the family. The proband (II-2) inherited hemizygous variation (c.1718G > A). The proband's mother (I-2) carried the c.1718G > A heterozygous variant, but this gene was normal in the proband's father (I-1) and younger brother (II-3); (B) Partial DNA sequences in the ATP7B gene of the family. The proband carried the homozygous mutation (c.2975C > T). The proband's father, mother, and younger brother carried the c.2975C > T heterozygous variants.
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F3
The results showed that the same heterozygous COL4A5 variant was detected in his mother (Figure 3A). The same heterozygous missense mutation of ATP7B was detected in his parents and younger brother (Figure 3B).
Timeline of clinical course, diagnostics, and treatment regimen of the patient. WES, whole-exome sequencing; AS, Alport syndrome; and WD, Wilson's disease.
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F4
A timeline of the clinical course, diagnostics, and treatment regimen of the patient are summarized in Figure 4.