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Abstract: TH-PO534

Identification of Novel Mutations and Phenotype in the Steroid Resistant Nephrotic Syndrome Gene NUP93

Session Information

  • Trainee Case Reports - I
    October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Sandokji, Ibrahim, Yale University School of Medicine, New Haven, Connecticut, United States
  • Marquez, Jonathan, Yale University School of Medicine, New Haven, Connecticut, United States
  • Ji, Weizhen, Yale University School of Medicine, New Haven, Connecticut, United States
  • Konstantino, Monica, Yale University School of Medicine, New Haven, Connecticut, United States
  • Lakhani, Saquib, Yale University School of Medicine, New Haven, Connecticut, United States
  • Khokha, Mustafa, Yale University School of Medicine, New Haven, Connecticut, United States
  • Warejko, Jillian Kateri, Yale University School of Medicine, New Haven, Connecticut, United States
Introduction

In 11-30% of steroid-resistant nephrotic syndrome (SRNS), a known gene mutation can be detected. NUP93 is a widely expressed gene that encodes a highly conserved nuclear pore protein that has been shown to cause non-syndromic autosomal recessive focal segmental glomerulosclerosis (FSGS). Here we describe a case of novel NUP93 mutations in a child with a syndromic SRNS phenotype.

Case Description

We identified compound heterozygous mutations of NUP93 gene using whole exome sequencing (WES) in a patient presented with syndromic SRNS and progressed to ESRD in her first decade of life. An African American and Hispanic 5-year-old girl presented with nephrotic syndrome, including nephrotic-range proteinuria (UPC of >29 mg/mg), edema, and hypoalbuminemia. She was clinically fluid overloaded, hypertensive, and quickly became anuric and required renal replacement therapy. She had signs of chronic kidney disease including hyperparathyroidism, anemia, and short stature. A urinalysis 1 year prior showed 3+ proteinuria that was not quantified. In addition to her kidney involvement, she had developmental delay with autistic features; including delays in expressive language, fine motor, social communication and repetitive hand movements. Additionally, she had two episodes of heart failure requiring inotropic support after having adequate dialysis for more than a month. Her echo showed systolic and diastolic dysfunction (ejection fraction as low as 35%) and dilated cardiomyopathy features of unclear etiology that did improve with aggressive nutritional support and blood pressure management.

Discussion

We detected compound heterozygous mutations in NUP93 a maternal missense mutation (ch16:56855426 A>G) c.206A>G, p.Y69C and a paternal nonsense mutation (ch16:56868107 C>G) c.1236C>G, p.Y412X. The mutations were highly conserved through phylogeny and had high pathogenicity prediction scores. We describe in this case novel mutations in the SRNS gene NUP93 resulting in a syndromic phenotype with neurologic and cardiac features. It remains unclear the degree to which NUP93 contributed to her cardiomyopathy, as this gene has also been described as localizing to cilia as well as the nucleoporin. WES is the ideal test for patients with SRNS as a conclusive molecular diagnosis does influence therapeutic choices.