High Rate of Mutations of Adhesion Molecules and Extracellular Matrix Glycoproteins in Patients with Adult-Onset Focal and Segmental Glomerulosclerosis.
Sara MarcosEmilio Rodrigo-CalabiaIgnacio VarelaMichal ČervienkaJavier Freire SalinasJosé Javier Gómez RománPublished in: Biomedicines (2023)
(1) Background: Focal and segmental glomerulosclerosis (FSGS) is a pattern of injury that results from podocyte loss in the setting of a wide variety of injurious mechanisms. These include both acquired and genetic as well as primary and secondary causes, or a combination thereof, without optimal therapy, and a high rate of patients develop end-stage renal disease (ESRD). Genetic studies have helped improve the global understanding of FSGS syndrome; thus, we hypothesize that patients with primary FSGS may have underlying alterations in adhesion molecules or extracellular matrix glycoproteins related to previously unreported mutations that may be studied through next-generation sequencing (NGS). (2) Methods: We developed an NGS panel with 29 genes related to adhesion and extracellular matrix glycoproteins. DNA was extracted from twenty-three FSGS patients diagnosed by renal biopsy; (3) Results: The average number of accumulated variants in FSGS patients was high. We describe the missense variant ITGB3 c.1199G>A, which is considered pathogenic; in addition, we discovered the nonsense variant CDH1 c.499G>T, which lacks a Reference SNP (rs) Report and is considered likely pathogenic. (4) Conclusions: To the best of our knowledge, this is the first account of a high rate of change in extracellular matrix glycoproteins and adhesion molecules in individuals with adult-onset FSGS. The combined effect of all these variations may result in a genotype that is vulnerable to the pathogenesis of glomerulopathy.
Keyphrases
- extracellular matrix
- end stage renal disease
- chronic kidney disease
- peritoneal dialysis
- ejection fraction
- newly diagnosed
- healthcare
- genome wide
- prognostic factors
- copy number
- escherichia coli
- biofilm formation
- patient reported outcomes
- staphylococcus aureus
- endothelial cells
- circulating tumor
- autism spectrum disorder
- patient reported
- cell migration
- circulating tumor cells