Exploring genotype-phenotype correlation in nucleoporin nephropathy.

Area of Science:

• Pediatric Nephrology
• Medical Genetics
• Rare Diseases

Background:

• Nucleoporin nephropathy is a poorly understood genetic kidney disorder with early childhood onset.
• Characterizing this rare condition is crucial for timely diagnosis and management.

Purpose of the Study:

• To analyze clinical and genetic data of pediatric patients with nucleoporin nephropathy.
• To review global cases and identify patterns in disease presentation, progression, and outcomes.

Main Methods:

• Retrospective analysis of pediatric patients from a southern Chinese center.
• Systematic review of globally reported nucleoporin nephropathy cases up to July 2024.

Main Results:

• Five pediatric cases showed early-onset disease, progressing to end-stage kidney disease (ESKD).
• Globally, 76.6% presented with nephrotic syndrome unresponsive to treatment; 89.4% progressed to ESKD.
• Neurological symptoms varied by genotype; East Asian patients often had specific mutations and fewer extrarenal symptoms.

Conclusions:

• Routine nucleoporin gene testing is advised for Asian children with steroid-resistant nephrotic syndrome or ESKD.
• Kidney transplantation shows good outcomes, but managing extrarenal symptoms remains challenging.
• Understanding genotype-phenotype correlations is key for improved management of nucleoporin nephropathy.