Podocytic and Endothelial Infolding in Focal Segmental Glomerulosclerosis with INF2 Mutation
- Glomerular Diseases: Podocyte Biology - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1403 Podocyte Biology
- Yang, Tingting, Chengdu First People's Hospital, Chengdu, Sichuan, China
- Zhu, Jianhua, Chengdu First People's Hospital, Chengdu, Sichuan, China
Podocytic infolding glomerulopathy (PIG) is characterized by podocyte cell invading into the GBM and intra-GBM spherules with around 40 reports only. The invaginations of endothelial cells to the GBM were generally not described. We report the specific ultrastructure of endothelial cells evidently invading into the GBM besides podocytes of a 25-year-old woman with the inverted formin-2 (INF2) mutation.
The patient presented as nephrotic syndrome whithout autoimmune disorders. Light microscopy of kidney biopsy showed the basement membrane was irregularly thickened (Figure 1(A-B)). Electron microscopy revealed diffuse irregular thickening of the basement membrane with podocyte foot-process infolding into and with many microspheres, some membrane like structures and a few electron-dense deposits inside (Figure 1(C-F)). Notably, villous cytoplasmic protrusion of endothelial cells were more conspicuous in the GBM.The gene sequencing showed novel heterozygous mutations in the INF2 gene (NM_022489.4). The c.395T>C mutation was classified as significance undetermined. The patient is stable with olmesartan and diuretics.
The pathogenesis of PIG remains unclear. In particular, villous protrusions of endothelial cells were more remarkable in the GBM in our case, suggesting that endothelial cells may be related to PIG. When the GBM is injured, the disordered skeletal structure may also easily trap the decomposing podocyte or endothelial cell processes in and dissociate them. Genetic mutations may also be involved in PIG. Whether the c.395T>C mutation had connection with PIG remains unclear. To our knowledge, this is one of the minority reported cases of PIG with gene detection. The specific pathogenesis and genetic explanation of PIG still needs to be further explored.
LM and EM of kidney biopsy specimen