Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with resistance to immunosuppression

Sabrina Giglio, Aldesia Provenzano, Benedetta Mazzinghi, Francesca Becherucci, Laura Giunti, Giulia Sansavini, Fiammetta Ravaglia, Rosa Maria Roperto, Silvia Farsetti, Elisa Benetti, Mario Rotondi, Luisa Murer, Elena Lazzeri, Laura Lasagni, Marco Materassi, Paola Romagnani

Research output: Contribution to journalArticlepeer-review


In children, sporadic nephrotic syndrome can be related to a genetic cause, but to what extent genetic alterations associate with resistance to immunosuppression is unknown. In this study, we designed a custom array for next-generation sequencing analysis of 19 target genes, reported as possible causes of nephrotic syndrome, in a cohort of 31 children affected by sporadic steroid-resistant nephrotic syndrome and 38 patients who exhibited a similar but steroid-sensitive clinical phenotype. Patients who exhibited extrarenal symptoms, had a familial history of the disease or consanguinity, or had a congenital onset were excluded. We identified a genetic cause in 32.3% of the children with steroid-resistant disease but zero of 38 children with steroid-sensitive disease. Genetic alterations also associated with lack of response to immunosuppressive agents in children with steroid-resistant disease (0% of patients with alterations versus 57.9% of patients without alterations responded to immunosuppressive agents), whereas clinical features, age at onset, and pathologic findings were similar in steroid-resistant patients with and without alterations. These results suggest that heterogeneous genetic alterations in children with sporadic forms of nephrotic syndrome associate with resistance to steroids as well as immunosuppressive treatments. In these patients, a comprehensive screening using such an array may, thus, be useful for genetic counseling and may help clinical decision making in a fast and cost-efficient manner.

Original languageEnglish
Pages (from-to)230-236
Number of pages7
JournalJournal of the American Society of Nephrology
Issue number1
Publication statusPublished - Jan 1 2015

ASJC Scopus subject areas

  • Nephrology


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