RT Journal Article
SR Electronic
T1 Heterogeneous Genetic Alterations in Sporadic Nephrotic Syndrome Associate with Resistance to Immunosuppression
JF Journal of the American Society of Nephrology
JO J. Am. Soc. Nephrol.
FD American Society of Nephrology
SP 230
OP 236
DO 10.1681/ASN.2013111155
VO 26
IS 1
A1 Giglio, Sabrina
A1 Provenzano, Aldesia
A1 Mazzinghi, Benedetta
A1 Becherucci, Francesca
A1 Giunti, Laura
A1 Sansavini, Giulia
A1 Ravaglia, Fiammetta
A1 Roperto, Rosa Maria
A1 Farsetti, Silvia
A1 Benetti, Elisa
A1 Rotondi, Mario
A1 Murer, Luisa
A1 Lazzeri, Elena
A1 Lasagni, Laura
A1 Materassi, Marco
A1 Romagnani, Paola
YR 2015
UL http://jasn.asnjournals.org/content/26/1/230.abstract
AB 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.