Manuela Schirru
High throughput sequencing in sporadic forms of steroid-resistant nephrotic syndrome: heterogeneous genetic alterations can predict resistance to treatments
S. Giglio
2014-01-01
Abstract
Steroid-resistant nephrotic syndrome (SRNS) is a disorder that results in end-stage renal disease and can be potentially related to a genetic cause, especially when it occurs in children. However, because of genetic heterogeneity, the real burden of genetic alterations in sporadic cases is unknown. In this study, we explored the possibility that genetic alterations of podocyte’s structure may explain lack of response to steroid treatment in children affected by sporadic childhood-onset nephrotic syndrome (NS), not only in a causative manner, but also as critical disease modifiers that influence response to steroid treatment and immunosuppressive agents. We designed a custom sequencing array to target all exons and part of flanking sequences for known podocyte genes responsible for SRNS, that was applied through next generation sequencing to a selected cohort of 50 patients with sporadic NS and variable response to steroid treatment. We identified a genetic cause in 40% of the 19 SRNS patients analysed. Modifier genes were observed in an additional 25% of patients exhibiting resistance to steroid, but nor disease causing neither disease modifier genes were observed in podocyte’s genes of 30 additional children that were sensitive to steroids. Treatment with immunosuppressive agents was effective only among patients that were negative to the test, while none of the patients displaying genetic alterations responded to any immunosuppressive agent. The results of this study suggest that in children affected by sporadic NS, resistance to steroid treatment may be related to genetic alterations in genes that control structure and function of the podocyte.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.