# Adult-Onset Nephrotic Syndrome and Optic Nerve Atrophy Associated With NUP93 Mutation

## TL;DR

A 25-year-old patient with kidney disease and optic nerve atrophy was found to have NUP93 gene mutations, linking kidney and eye issues for the first time.

## Contribution

This is the first reported case linking NUP93 mutations to optic nerve atrophy alongside nephrotic syndrome.

## Key findings

- The patient had biallelic class 4, likely pathogenic variants in the NUP93 gene.
- The case suggests a non-coincidental association between NUP93 mutations, optic nerve atrophy, and steroid-resistant nephrotic syndrome.
- Genetic testing is highlighted as essential in patients with syndromic features and kidney disease.

## Abstract

Focal segmental glomerulosclerosis (FSGS) represents one of the most common etiologies of nephrotic syndrome. In 10% to 20% of cases, it is associated with steroid resistance and has the potential to progress to kidney failure. Compound heterozygote or homozygote mutations in the NUP93 gene have been associated with FSGS-related nephrotic syndrome. To the best of our knowledge, no case of NUP93 related FSGS has presented in the literature with associated ophthalmological anomaly. In this report, we present the case of a 25-year-old White patient who presented with rapidly progressive chronic kidney disease, congenital bilateral optic nerve atrophy and steroid-resistant nephrotic syndrome. Kidney biopsy showed FSGS with more than 80% foot process effacement on electronic microscopy. Genetic testing by means of whole exome sequencing later showed the presence of biallelic class 4, likely pathogenic variants in the NUP93 gene. Although we cannot exclude another cause, such as a genetic defect outside the genomic regions screened by our exome analyses, for the bilateral optic atrophy observed in our patient, this suggests that this association is not coincidental. Our case report highlights the importance of genetic testing in cases of steroid-resistant nephrotic syndrome that present with syndromic congenital features.