Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 6:1139–1148

Background and objectives The increasing number of podocyte-expressed genes implicated in steroid-resis-tant nephrotic syndrome (SRNS), the phenotypic variability, and the uncharacterized relative frequency of mutations in these genes in pediatric and adult patients with SRNS complicate their routine genetic analy-sis. Our aim was to compile the clinical and genetic data of eight podocyte genes analyzed in 110 cases (125 patients) with SRNS (ranging from congenital to adult onset) to provide a genetic testing approach. Design, setting, participants, & measurements Mutation analysis was performed by sequencing the NPHS1, NPHS2, TRPC6, CD2AP, PLCE1, INF2, WT1 (exons 8 and 9), and ACTN4 (exons 1 to 10) genes. Results We identified causing mutations in 34 % (37/110) of SRNS patients, representing 67 % (16/24) famil-ial and 25 % (21/86) sporadic cases. Mutations were detected in 100 % of congenital-onset, 57 % of infantile-onset, 24 and 36 % of early and late childhood-onset, 25 % of adolescent-onset, and 14 % of adult-onset pa-tients. The most frequently mutated gene was NPHS1 in congenital onset and NPHS2 in the other groups. A partial remission was observed in 7 of 26 mutation carriers treated with immunosuppressive agents and/or angiotensin-converting enzyme inhibitors. Patients with NPHS1 mutations showed a faster progres-sion to ESRD than patients with NPHS2 mutations. None of these mutation carriers relapsed after kidney transplantation. Conclusions We propose a genetic testing algorithm for SRNS based on the age at onset and the familial/ sporadic status. Mutation analysis of specific podocyte-genes has a clinical value in all age groups, espe-cially in children