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Abstract: SA-PO538

Copy Number Variation Analysis in 138 Families With Steroid-Resistant Nephrotic Syndrome Identifies Homozygous Causal Deletions in PLCE1 and NPHS2 in Two Families

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic


  • Pantel, Dalia, Boston Children’s Hospital, Boston, United States
  • Mertens, Nils David, Boston Children’s Hospital, Boston, Massachusetts, United States
  • Schneider, Ronen, Boston Children’s Hospital, Boston, Massachusetts, United States
  • Kari, Jameela Abdulaziz, King Abdulaziz University, Faculty of Medicine, Jeddah, Saudi Arabia
  • El desoky, Sherif Mohamed, King Abdulaziz University, Faculty of Medicine, Jeddah, Saudi Arabia
  • Bagga, Arvind, Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
  • Lim, Tze Yin, Division of Nephrology, Columbia University, New York City, New York, United States
  • Shril, Shirlee, Boston Children’s Hospital, Boston, Massachusetts, United States
  • Hildebrandt, Friedhelm, Boston Children’s Hospital, Boston, Massachusetts, United States

Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of end-stage renal disease in children and adults under the age of 20 years. Previously, we were able to detect by whole-exome sequencing (WES) a known monogenic cause of SRNS in 25% of affected families (Warejko CJASN 13:53, 2018), supporting the indispensable role of WES in uncovering genetic causation of the syndrome. However, WES falls short of detecting copy number variations (CNV) due to technical challenges. We therefore hypothesized that causal CNVs could be detected in a large SRNS cohort.


We performed genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on a cohort of 138 SRNS families, in which we previously did not identify a genetic cause through WES. We evaluated WES and CNV data for variants in 61 known SRNS genes and in 12 genes, in which variants are known to cause a phenocopy of SRNS. We applied previously published, predefined criteria to evaluate and classify the CNVs.


In a cohort of 138 families with SRNS, we detected a novel CNV in two genes in two families (2/138 families, 1.5%) after having excluded competing variants by genome-wide WES and CNV analysis. Both CNVs are homozygous deletions: We detected a deletion of 9,670 bp in the PLCE1 gene and a deletion of 6,790 bp in the NPHS2 gene. The deletions were confirmed across breakpoint using PCR and Sanger sequencing.


This study shows that CNV analysis can identify the genetic cause in families with SRNS in which a genetic cause was not found through WES, though the rate of detected CNVs lies below the one found in other monogenic kidney diseases, like congenital anomalies of the kidneys and urinary tract.


  • Other NIH Support