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. 2011 May;6(5):1139-48.
doi: 10.2215/CJN.05260610. Epub 2011 Mar 17.

Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome

Sheila Santín  1 , Gemma Bullich, Bárbara Tazón-Vega, Rafael García-Maset, Isabel Giménez, Irene Silva, Patricia Ruíz, José Ballarín, Roser Torra, Elisabet Ars
Affiliations

Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome

Sheila Santín et al. Clin J Am Soc Nephrol. 2011 May.

Abstract

Background and objectives: The increasing number of podocyte-expressed genes implicated in steroid-resistant 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 analysis. 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) familial 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 patients. 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 progression 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, especially in children.

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Figures

Figure 1.
Figure 1.
Age at diagnosis of NS in correlation to detected pathogenic mutations in NPHS1, NPHS2, WT1, TRPC6, and INF2 in 110 families (we did not include the ACTN4 and CD2AP genes because no pathogenic mutations were identified in our cohort). (A) Familial and sporadic cases. (B) Percentage of mutations in familial cases. (C) Percentage of mutations in sporadic cases.
Figure 2.
Figure 2.
Genetic approach in children and adults with SRNS.
See this image and copyright information in PMC

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