Chapter 4 74 (56). Cross-striated fibrils with a diameter of 140 nm and regular periodicity were found in the mesangial area and the laminae rarae of the glomerular basement membrane of the native kidney (Figure 4). This was the only patient in the cohort for whom EM data was available. Genetic data of this patient was not available. Figure 4. Glomerular fibril deposition HME-MO glomerulopathy (A and B) Deposition of large fibrils with a diameter of 140 nm was seen in the glomerulus of an MO patient. The fibril depositions are seen in the laminae rarae of the GBM and in the mesangium. (c) General morphology is disrupted due to the fibril deposition. In figure B, endothelial lumen (a) and fenestrated endothelial cells can be seen (b). The fibrils in the GBM appear to be collagenous in nature. (c) Scale bar = 5 µm. Discussion In this study, we investigated the effect of heterozygous EXT1 or EXT2 germline mutations on glomerular permeability, glomerular morphology, and the endothelial glycocalyx. No (micro)albuminuria was observed in these patients, despite also having a higher prevalence of other risk factors for developing proteinuria with more hypertension, diabetes and NSAID use, as shown in Table 1. Furthermore, no specific glomerular morphological changes were observed in biopsies from a historic cohort of MO patients without clinical symptoms of renal damage. However, one of MO patient with renal pathology showed a glomerular phenotype resembling MO glomerulopathy. No significant difference was found in PBR thickness or vascular density between MO patients and controls. This study shows that heterozygous EXT1 or EXT2 germline mutations do not significantly influence glomerular permeability or the endothelial glycocalyx. Glomerular permeability was not affected by these mutations, as no difference was found in albuminuria between
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