PMC6287602_01
Light microscopic findings. a: Most glomeruli showed segmental infiltration of foam cells in the capillary lumen (black arrows). b: Sudan III-positive staining for lipid (black arrows) is observed in the mesangium and infiltrating foam cells (original magnification x 400). c: In higher magnification, PAM staining revealed partial double contour formation and spike-like lesions (white arrows). d: PAM staining revealed partial bubble-type appearance (white arrows).
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Figure1
Most glomeruli showed segmental sclerosis, infiltration of foam cells containing lipid deposits in capillary lumen (Figure 1a). In periodic methenamine silver (PAM)-stained sections, spike formation and bubbling were detected on the glomerular basement membrane (GBM) (Figure 1c, d). III staining was strongly positive not only in the mesangial and infiltrating foam cells but also in the focal capillary lumen in the glomerulus (Figure 1b). Immunofluorescence (IF) studies demonstrated subtle granular staining for IgG along the capillary wall; however, C3 was not detected (data not shown). The patient's sample showed the position of ApoE2/2 (Figure 4a, Lane 1).  Genotype epsilon2/2 in the patient was identified by 91- and 83-bp fragments (Figure 4b, Lane 1).
Electron microscopic findings. a: EDDs were observed in subepithelial lesion with membranous nephropathy-like spike formation of the basement membrane (x 2,500). b: Highly-magnified subepithelial position ( ) (x 200,000).
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Figure2
Highly-dense deposits accompanied by spike formation identical to MN were seen in the subepithelial area (Figure 2a, b).
Electron microscopic findings. a: EDDs with various sizes and densities were observed also in the subendothelial lesions. Severe effacement of podocytes was noted (x 2,500). The capillary lumen was filled with lipid deposits that did not show a lamellar formation (  ). b: In higher magnification, EDDs with a high density consist of microbubbles or microcysts (   ) (x 200,000).
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Figure3
EDDs were detected but in higher magnification, and microbubbles were contained (Figure 3a, b). Effacement of foot process was also accompanied with these depositions.
Phenotype, genotype, and DNA sequence of ApoE in this patient. a: ApoE phenotype analysis. The patient was identified as E2/2 (lane 1). Controls (lanes 2, 3, and 4) show E2/3, E3/3, and E3/4, respectively. b: APOE genotype analysis by RFLP using HhaI as a restriction enzyme. The patient was identified as epsilon2/2. Controls (lanes 2, 3, and 4) show epsilon2/2, epsilon3/4, and epsilon3/3, respectively. c: RFLP for ApoE Toyonaka using SacI as a restriction enzyme. Lanes M, 1, 2, and 3 show marker, PCR only, the patient (ApoE Toyonaka), and normal control, respectively. d: Sequence analysis of APOE gene. A heterozygous missense mutation (c.644 C>G) in exon 4 leads to an amino acid substitution Cys (TGC, lower) for Ser (TCC, upper) at codon 197.
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Figure4
The patient's sample showed the position of ApoE2/2 (Figure 4a, Lane 1).  Genotype epsilon2/2 in the patient was identified by 91- and 83-bp fragments (Figure 4b, Lane 1). The ApoE Toyonaka (Ser197Cys) as shown in Figure 4d was also confirmed by RFLP analysis digested with SacI (Figure 4c). Arg158Cys) (data not shown) and a heterozygous missense mutation (C to G) in exon 4 leading to an amino acid substitution Cys (TGC) for Ser (TCC) at codon 197 (c.644 C>G: p.S215C: Ser197Cys) (Figure 4d). All these findings were the same as that of a previous case of ApoE2/2 and ApoE Toyonaka showing MN-like glomerular histology [6]. 