Abstract: FR-PO0938
Genetic Analysis of Pediatric Patients Registered in the Brazilian Network for Childhood Nephrotic Syndrome
Session Information
- Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Watanabe, Andreia, Universidade de Sao Paulo, São Paulo, SP, Brazil
- Feltran, Luciana S., Hospital Samaritano de Sao Paulo, São Paulo, SP, Brazil
- Ribeiro Nogueira, Beatriz, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
- Belangero, Vera Santoro, Universidade Estadual de Campinas, Campinas, SP, Brazil
- Varela-Calais, Patricia, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Pesquero, Joao Bosco, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
- Koch Nogueira, Paulo C., Hospital Samaritano de Sao Paulo, São Paulo, SP, Brazil
- Onuchic, Luiz F., Universidade de Sao Paulo, São Paulo, SP, Brazil
- Guaragna, Mara S., Universidade Estadual de Campinas, Campinas, SP, Brazil
Group or Team Name
- REBRASNI
Background
Up to 43.5% of pediatric steroid-resistant nephrotic syndrome (SRNS) cases have a monogenic cause, while genetic screening is limited in Brazil.
Methods
The Brazilian Network for Childhood Nephrotic Syndrome (REBRASNI) has a website for inclusion of patients with idiopathic NS. Criteria for WES include SRNS, with priority to chronic kidney disease (CKD) stages 3-5, NS onset <2 years of age, familial kidney disease, and/or syndromic features. Variants of 79 SRNS-associated genes were analyzed according to ACMG.
Results
From 04/2019-02/2026, 138/330 registered cases were classified as SRNS. CKD stages 3-5 were present in 60/138, age of NS onset <2 years in 49, and familial glomerular disease in 14, yielding 113 selected patients. Only 40 were sequenced because of unreachness (40), post-kidney transplantation (KT) recurrence (9), death (7), and other reasons (17). Among the sequenced cases, age of NS onset was 2.4 (IQR 1.3-4.0) years, 42.5% were White and 35% male. No consanguinity was declared and 7/40 had family history of CKD. Kidney biopsy (KB) was performed in 28/40, showing focal segmental glomerulosclerosis (FSGS) (11), minimal change disease (11), diffuse mesangial sclerosis (2), other diagnoses (3), and non-representative sample (1). Genetic cause was found in 8/40 (20%) patients:
- NPHS1:c.515_517delAAC:p.(Thr172del) and c.90del:p.(Arg32Glyfs*10), both in homozygosity in 2 children with congenital NS;
- COL4A5:c.4309C>T:p.(Gln1437*) in a male with NS at age 14 with hematuria, FSGS and hearing impairment
- LAMB2:c.835_851del:p.(Val279Leufs*19) and c.4573+5G>A in a boy with NS at 9 months and ocular defects consistent with Pierson's disease;
- PAX2:c.496+1G>C in heterozygosity in a girl with nephrotic range proteinuria detected at age 13 and CKD family history;
- LMX1B:c.737G>A,p.(Arg246Gln) in heterozygosity, previously described in isolated FSGS;
- AVIL:c.595C>T,p.(Arg199*) and c.2221-10T>C in a girl with non-recurring NS post-KT.
- A patient with APOL1 G1/G1 had NS onset at 11 months, FSGS on KB and complete remission with calcineurin inhibitor.
Conclusion
The high prevalence of SNCR in registered children likely resulted from WES availability. The frequency of monogenic causes is consistent with the data of previous Brazilian cohorts. The REBRASNI WES initiative will likely increase the inclusion of cases, potentially bringing great contribution to the pediatric NS field.
Acknowledgment
We thank ICRIM for their financial support of the WES project.
Funding
- Private Foundation Support