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Abstract: SA-PO539

Biallelic Variants in NUP85 Causes Pediatric Steroid Resistant Nephrotic Syndrome

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

Authors

  • Rossanti, Rini, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Japan
  • Hilmanto, Dany, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Japan
  • Horinouchi, Tomoko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Japan
  • Sakakibara, Nana, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Japan
  • Nagano, China, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Japan
  • Yamamura, Tomohiko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Japan
  • Ishiko, Shinya, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Japan
  • Aoto, Yuya, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Japan
  • Kondo, Atsushi, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Japan
  • Iijima, Kazumoto, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan, Japan
  • Nozu, Kandai, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Japan
Introduction

Steroid resistant nephrotic syndrome consistently progressed to end-stage renal disease. Despite the fact that more than 50 monogenic causes of steroid resistant nephrotic syndrome (SRNS) have been identified, a large proportion of SRNS remains unexplained. Nucleoporin 85, a protein encoded by the inner ring subunit of the nuclear pore complex (NPC), has recently been found to cause SRNS. Here we describe a NUP85 compound heterozygous mutation in a child with focal segmental glomerulosclerosis (FSGS). Although one was a large deletion variant with obvious pathogenicity, another was a novel heterozygous variant which pathogenicity was unknown. To verify the pathogenicity of the missense variant, we conducted in vitro protein expression analyses.

Case Description

A 9-year-old girl with learning disorder and low vision was diagnosed with SRNS at 3 years old without any history of kidney disease in the family. The histological finding was FSGS. Pre-emptive kidney transplantation was conducted at 9 years-old. Patient harbored 2 novel heterozygous mutations in NUP85, c.1379G>A (p.Arg460Gln) in exon 14 by next generation sequencing, and a large deletion straddling from intron 11 of NUP85 to GGA3 gene by copy number variant analysis and custom array CGH. The in vitro protein expression analysis showed abnormal localization of NUP85 in cytoplasm with the particle formation by the missense variant.

Discussion

In this study we defined the pathogenicity of a very rare missense variant in NUP85. This finding can help identifying more variants in this rare form of SRNS.