b01ee921-4db9-4955-8dbe-0c5cddff8fc3
Glomerulosclerosis genetic characterization
Focal and segmental glomerulosclerosis (FSGS) is one of the most frequent causes of adult nephrotic syndrome, 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). Methods: We have developed a NGS panel with 29 genes related with adhesion and extracellular matrix glycoproteins. DNA extracted from twenty-three patients with FSGS, demonstrated by renal biopsy was analyzed for the presence of variants in sequence; Results: Of the 29 genes studied, we found DNA variants in 27 in all patients. 91% of mutations were of uncertain significance (VUS) or pathogenic type; Conclusions: To the best of our knowledge this is the first report of a high rate of alterations in adhesion molecules and extracellular matrix glycoproteins in adult-onset FSGS patients. The sum effect of all the variants could help to the FSGS development, or produce, to a greater or lesser extent, a genotype susceptible to the glomerulopathy pathogenesis.
Focal and segmental glomerulosclerosis (FSGS) is one of the most frequent causes of adult nephrotic syndrome, 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). Methods: We have developed a NGS panel with 29 genes related with adhesion and extracellular matrix glycoproteins. DNA extracted from twenty-three patients with FSGS, demonstrated by renal biopsy was analyzed for the presence of variants in sequence; Results: Of the 29 genes studied, we found DNA variants in 27 in all patients. 91% of mutations were of uncertain significance (VUS) or pathogenic type; Conclusions: To the best of our knowledge this is the first report of a high rate of alterations in adhesion molecules and extracellular matrix glycoproteins in adult-onset FSGS patients. The sum effect of all the variants could help to the FSGS development, or produce, to a greater or lesser extent, a genotype susceptible to the glomerulopathy pathogenesis.