Abstract: SA-PO588
Genetic Findings in Adults with Sporadic Steroid-Resistant Nephrotic Syndrome
Session Information
- Noncystic Mendelian Diseases
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Genetic Diseases of the Kidney
- 802 Non-Cystic Mendelian Diseases
Authors
- Servais, Aude, Necker University Hospital, Paris, France
- Gribouval, Olivier, Imagine Institute, Paris Descartes University, Paris, France
- Boyer, Olivia, Necker University Hospital, Paris, France
- Hummel, Aurelie, Necker University Hospital, Paris, France
- Dantal, Jacques, Institut de Transplantation Urologie Néphrologie, Nantes, France
- Tête, Marie-Josèphe, Imagine Institute, Paris Descartes University, Paris, France
- Antignac, Corinne, Imagine Institute, Paris Descartes University, Paris, France
Background
In recent years, proposals for genetic screening paradigms in Steroid-Resistant Nephrotic Syndrome (SRNS) preferentially addressed congenital, infantile onset and familial cases. Sporadic SRNS/FSGS adult patients are currently only tested for the NPHS2 nonneutral p.R229Q polymorphism. To uncover the distribution of disease-causing gene mutations in an adult sporadic FSGS/SRNS population, we used a NGS panel in a cohort of adult patients.
Methods
We selected adult patients (age at onset of proteinuria above 18 years), with non syndromic biopsy proven FSGS and/or SRNS, without known family history. We used strict clinical criteria including no response to glucocorticoids but also to cyclosporine and no relapse after renal transplantation. We applied a NGS panel covering 37 genes to 135 unrelated patients.
Results
Mean age at onset of proteinuria was 30.1 (18.1-84.0) years. Eighteen (13.3%) presented with mutation (15/135, 11.1%) or variant of unknown significance (VOUS) (3/135, 2.2%) in known monogenic SRNS genes and 14 (10.4%) with APOL1 high risk allele. We identified 11 novel mutations including mutations in PAX2, INF2, NPHS2, MYO1E, and CD2AP genes. Collagen mutations represented 38.8% of all mutations. Mean age at onset of proteinuria was lower in the group with mutations than in patients with no mutation or APOL1 risk variant (24.9±7.9 vs 30.9±11.7, p=0.01). Mutations in non collagen genes were all found in patients younger than 30 years of age, whereas mutations in collagen genes were also identified in older patients until 50 years of age. Patients with mutations presented with lower eGFR at diagnosis (43.6±31.8 vs 87.4± 34.8 ml/min/1.73m2, p=0.006), reflecting a more severe disease. Age at ESRD was higher in patients with mutations in collagen genes than in patients with mutations in other genes (47.5±1.6 vs 26.6±4.6 years, p=0.01).
Conclusion
We identified a mutation or a VOUS in known monogenic SRNS genes in 13.3% of patients and APOL1 high risk allele in 10.4%. Collagen mutations causing Alport Disease were the more frequent identified mutations.
Funding
- Government Support - Non-U.S.