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Publications

Journal Article Ahead of print

PubMed: 41575523 DOI: 10.1007/s00467-026-07151-7

Identification of monogenic variants in steroid-resistant and steroid-sensitive nephrotic syndrome.

Pediatr Nephrol

Authors: Bshara Mansour, Katharina Lemberg, Ronen Schneider, Ken Saida, Izzeldin Elmubarak, Seyoung Yu, Kirollos Yousef, Camille Nicolas Frank, Korbinian M Riedhammer, Muhammad Yasir Zahoor, Caroline M Kolvenbach, Lea M Merz, Nils D Mertens, Aaron Bao, Daanya Salmanullah, Gina Kalkar, Selina Hölzel, Elena Zion, Daniel Marchuk, Kraisoon Lomjansook, Alina Braun, Gijs A C Franken, Loai A Eid, Hazem Subhi H Awad, Muna Al Saffar, Neveen A Soliman, Marwa M Nabhan, Jameela A Kari, Sherif El Desoky, Mohamed A Shalaby, Said Ooda, Hanan M Fathy, Shrikant Mane, Shirlee Shril, Michael J G Somers, Florian Buerger, Friedhelm Hildebrandt

Affiliations

  • Department of Pediatrics, Division of Nephrology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, 02115 MA, USA.
  • Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne and University Hospital Cologne, Cologne, Germany.
  • Department of Nephrology, Klinikum Rechts Der Isar, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany.
  • Institute of Biochemistry & Biotechnology, University of Veterinary & Animal Sciences, Lahore, Pakistan.
  • Department of Pediatrics I, Medical Faculty, University Children's Hospital Heidelberg, Heidelberg University, Heidelberg, Germany.
  • Department of Pediatrics, University Hospital Leipzig, Leipzig, Germany.
  • Kidney Centre of Excellence, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates.
  • Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab , Emirates University, Abu Dhabi, United Arab Emirates.
  • Department of Pediatrics, Center for Pediatric Nephrology and Transplantation, Kasr Al Ainy Medical School, Cairo University, Cairo, Egypt.
  • Egyptian Group for Orphan Renal Diseases (EGORD), Cairo, Egypt.
  • Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo, Egypt.
  • Pediatric Nephrology Center of Excellence, Department of Pediatrics, Faculty of Medicine, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Experimental and Clinical Internal Medicine Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
  • Department of Pediatrics, Alexandria Faculty of Medicine, Alexandria University, Alexandria, Egypt.
  • Department of Pediatrics, Farwaniya Hospital, Ministry of Health, Sabah Al Nasser, Kuwait.
  • Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
  • University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Department of Pediatrics, Division of Nephrology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, 02115 MA, USA.

Abstract

BACKGROUND

Steroid-resistant nephrotic syndrome (SRNS) constitutes the second most common cause of chronic kidney disease (CKD) in children. A monogenic cause can be identified in approximately 25% of SRNS cases. In contrast, steroid-sensitive or steroid-dependent nephrotic syndrome (SSNS/SDNS) is typically attributed to multifactorial or immunological causes and rarely linked to monogenic etiology.

METHODS

We performed exome sequencing (ES) in 237 families, including 183 with SRNS and 54 with SSNS/SDNS.

RESULTS

A (likely) pathogenic variant in a known SRNS gene was identified in 29/183 individuals with SRNS (15.8%). Additionally, 6/183 (3.3%) individuals with SRNS carried pathogenic variants in phenocopy genes-genes associated with diseases that clinically mimic SRNS. The diagnostic yield was significantly higher in individuals with ≥ 50 Mb homozygosity-by-descent (HBD) (44.7% vs. 8.5%) and in those with SRNS disease onset before 1 year of age (41.9%). In individuals with SSNS/SDNS, we found a likely causative variant in only 1 of 54 probands.

CONCLUSIONS

A genetic cause was established in 19.1% of SRNS patients (15.8% in known SRNS genes and 3.3% in phenocopy genes), but only 1.9% of non-steroid-resistant cases.

MeSH

Kidney Diseases, Genes, Nephrotic Syndrome, Steroids