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Abstract: FR-PO663

Genotype-Phenotype Associations in Patients with Congenital and Infantile Nephrotic Syndrome

Session Information

  • Pediatric Nephrology - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology


  • Islam, Md Saimul, Texas Tech University Health Sciences Center, Amarillo, Texas, United States
  • Smoyer, William E., Nationwide Children's Hospital, Columbus, Ohio, United States
  • Mattoo, Tej K., Wayne State University School of Medicine, Detroit, Michigan, United States
  • Myette, Robert L., Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
  • Wenderfer, Scott E., BC Children's Hospital Department of General Pediatrics, Vancouver, British Columbia, Canada
  • Kallash, Mahmoud, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Vasylyeva, Tetyana L., Texas Tech University Health Sciences Center, Amarillo, Texas, United States

Group or Team Name

  • Tetyana L. Vasylyeva.

Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) are disorders of the slit diaphragm of podocytes in the glomerular basement membrane. CNS manifests during the first three months of life, and INS between 3-12 months. The clinical features of the diseases include nephrotic-range proteinuria, hypoalbuminemia, and edema. The most common causes of CNS and INS are mutations in the NPHS1 and NPHS2 genes encoding nephrin and podocin, respectively. This study aimed to establish specific genetic characteristics of CNS and INS and their clinical correlations in the North American population.


Nine Pediatric Nephrology Research Consortium (PNRC) sites retrospectively reviewed charts of 36 patients born between 1998 and 2019 with CNS or INS and underwent genetic testing. ClinVar, SNP, and Human mutation database confirmed the mutation's pathogenicity.


NPHS1 mutations were more often seen in CNS patients (27/36; 75%), whereas the INS group had more frequent mutations of WT1 (3/11;27.2%) and NPHS2 (4/11;36.3%) genes. Among patients with NPHS1 mutations, the splice site had more mutations than the gene coding region, irrespective of the group. Among these mutations, IVS17-1 G>A splice mutation was found in 4 subjects that showed aggressive features of CNS. Interestingly, the mutation's pathogenicity was confirmed by ClinVar, SNP, and Human mutation database.
In patients with CNS, the frequency (9/18;50%) of multiple mutations of the NPHS1 gene was higher than in the INS group (2/5;40%) and significantly associated with hyperproteinemia (p=0.021) and hypoalbuminemia (p=0.03). Albumin infusions were much more effective in CNS patients with NPHS2/WT1 mutations than those with NPHS1 mutations. In INS patients with WT1 mutations, albumin infusions were less effective in supporting serum albumin levels.


Variations in splice sites, especially IVS17-1 G>A, and multiple mutations in the NPHS1 gene were associated with a more aggressive course of CNS in infants.