# A Novel NPHP5 Gene Mutation in Three Siblings With Nephronophthisis Without Retinitis Pigmentosa: A Case Report

## TL;DR

A new mutation in the NPHP5 gene is found in three siblings with kidney disease but without retinitis pigmentosa.

## Contribution

A novel IQCB1/NPHP5 gene variant is identified in a Saudi family without retinitis pigmentosa.

## Key findings

- A novel IQCB1/NPHP5 gene variant (p.Al a486Asp) was found in three siblings with nephronophthisis.
- The affected siblings and family members show autosomal recessive inheritance of the variant.
- The mutation is associated with kidney disease but not retinitis pigmentosa, differing from prior reports.

## Abstract

Nephronophthisis (NPHP) is a hereditary renal disorder characterized by the progression to end-stage renal disease (ESRD) at a young age. Our understanding of this disorder continues to improve as we identify more genes and gene variants associated with NPHP. In this report, we present a young patient with newly diagnosed advanced renal impairment and a strong family history of ESRD at a young age. The patient's kidney biopsy showed features suggestive of severe chronic interstitial nephritis, along with histopathological findings of advanced renal disease. Genetic testing revealed a novel variant in the IQCB1/NPHP5 gene, which is autosomal recessive. Family genetic analysis revealed that the patient's parents and two of his children are heterozygous for the identified variant, while two siblings with ESRD are homozygous for the IQCB1 p.(Ala486Asp) variant. Unlike previously described mutations in the IQCB1/NPHP5 gene, the patient and his affected siblings do not have retinitis pigmentosa. We report this novel gene variant in a Saudi family, describe its associated clinical features, and present the results of the family segregation analysis.