Abstract: TH-PO0605
Identification of a Monogenic Cause in Steroid-Resistant Nephrotic Syndrome and Related Kidney Diseases
Session Information
- Monogenic Kidney Diseases: Glomerular
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Mansour, Bshara, Boston Children's Hospital, Boston, Massachusetts, United States
- Lemberg, Katharina, Boston Children's Hospital, Boston, Massachusetts, United States
- Schneider, Ronen, Boston Children's Hospital, Boston, Massachusetts, United States
- Buerger, Florian, Boston Children's Hospital, Boston, Massachusetts, United States
- Saida, Ken, Boston Children's Hospital, Boston, Massachusetts, United States
- Yousef, Kirollos, Boston Children's Hospital, Boston, Massachusetts, United States
- Yu, Seyoung, Boston Children's Hospital, Boston, Massachusetts, United States
- Elmubarak, Izzeldin, Boston Children's Hospital, Boston, Massachusetts, United States
- Riedhammer, Korbinian M., Boston Children's Hospital, Boston, Massachusetts, United States
- Salmanullah, Daanya, Boston Children's Hospital, Boston, Massachusetts, United States
- Zahoor, Muhammad Y., Boston Children's Hospital, Boston, Massachusetts, United States
- Kalkar, Gina S, Boston Children's Hospital, Boston, Massachusetts, United States
- Zion, Elena, Boston Children's Hospital, Boston, Massachusetts, United States
- Marchuk, Daniel, Boston Children's Hospital, Boston, Massachusetts, United States
- Eid, Loai Akram, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates
- Soliman, Neveen, Alexandria University Faculty of Medicine, Alexandria, Alexandria Governorate, Egypt
- Nabhan, Marwa Mohamed, Alexandria University Faculty of Medicine, Alexandria, Alexandria Governorate, Egypt
- Kari, Jameela Abdulaziz, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia
- El Desoky, Sherif Mohamed, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia
- Shalaby, Mohamed Ahmed, King Abdulaziz University, Jeddah, Makkah Province, Saudi Arabia
- Fathy, Hanan, Alexandria University Faculty of Medicine, Alexandria, Alexandria Governorate, Egypt
- Mane, Shrikant M., Yale School of Medicine, New Haven, Connecticut, United States
- Shril, Shirlee, Boston Children's Hospital, Boston, Massachusetts, United States
- Somers, Michael J., Boston Children's Hospital, Boston, Massachusetts, United States
- Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States
Background
Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease in children and young adults. Significant progress in understanding its pathogenesis has been made through the identification of nearly 80 monogenic causes, which account for approximately 11-30% of SRNS cases with onset before the age of 25. In contrast, monogenic causes have been found only sporadically in steroid-sensitive or steroid-dependent nephrotic syndrome (SSNS/SDNS), where a multifactorial or immunological genesis is typically causative.
Methods
We conducted exome sequencing (ES) on a total of 299 families, including 183 families affected by SRNS and 116 families primarily with SSNS/SDNS.
Results
We identified a likely pathogenic variant in 35 out of 183 individuals with steroid-resistant nephrotic syndrome (SRNS), representing 19.1%, and in 7 out of 116 individuals with a non-SRNS phenotype (6%). Further analysis revealed pathogenic variants in phenocopy genes that mimic the clinical features of SRNS (COL4A3, COL4A5, FN1, and OCRL) in 8 of 183 participants (4.4%) and in 11 of 116 participants (9.5%) across the SRNS and non-SRNS cohorts, respectively. The detection rate was significantly higher in individuals with homozygosity-by-descent (HBD) of ≥50 Mb (50% vs. 11%) and in those with early onset of disease, with a 45% detection rate in individuals under 1 year of age.
Conclusion
We identified a genetic cause of kidney disease in 23.5% and 15.5% of SRNS and non-SRNS cohort, respectively. Although genetic detection rates in individuals with nephrotic range proteinuria who are not defined by steroid resistancy are less common, we still found likely deleterious variants in known SRNS genes in 6% of these cases. Given the significant implications of establishing a genetic diagnosis, genetic testing should be considered even for individuals with SSNS or SDNS.