Abstract
Steroid-resistant nephrotic syndrome (SRNS) is a paradigmatic disease to illustrate the major clinical consequences that can arise from genetic testing. Patients with pathogenic variants should be spared inefficient and potentially toxic immunosuppressive therapy; although a partial reduction of proteinuria has been reported with calcineurin inhibitors and/or renin-angiotensin-aldosterone inhibitors in a small number of cases. A better understanding of disease mechanisms may help identifying targeted therapeutic agents, and guide specific management of extra-renal features. Moreover, these patients have a very low risk of recurrence after kidney transplantation. Finally, such diagnosis is crucial for genetic counseling with respect to family planning but also to assess the suitability of relatives as organ donors. Next-generation sequencing approaches are increasingly used as the first step of genetic analyses. Causative pathogenic variants are identified in approximately 30% of children with SRNS and at least 66% in congenital and infantile cases. Among these genes, NPHS1 and NPHS2 are by far the two main autosomal recessive genes implicated in SRNS, while INF2 is the leading cause of autosomal dominant SRNS. Most novel gene variants are rare and involve few families. Moreover, NGS has revealed causative variants in unexpected genes such as ciliary or tubular genes and has widened the phenotypes associated with SRNS. More complex inheritance involving susceptibility variants, oligogenism or interallelic influence of variants have also been described as a cause of SRNS.
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Boyer, O., Gbadegesin, R., Waters, A. (2021). Clinical Aspects of Genetic Forms of Nephrotic Syndrome. In: Emma, F., Goldstein, S., Bagga, A., Bates, C.M., Shroff, R. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27843-3_91-1
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