Genotype/phenotype correlation in nephrotic syndrome caused by WT1 mutations

Area of Science:

• Nephrology
• Genetics
• Pediatric Oncology

Background:

• Nephrotic syndrome (NS) can arise from Wilms tumor 1 (WT1) gene mutations.
• The risk of developing Wilms tumor (WT) varies among patients with NS due to WT1 mutations.

Purpose of the Study:

• To describe the genotype/phenotype correlation in patients with NS caused by WT1 mutations.
• To analyze the outcome and WT risk based on specific WT1 mutation types.

Main Methods:

• Genotype analysis of 52 patients from 51 families with NS due to WT1 mutations.
• Categorization of mutations into KTS, missense, nonsense, intron 8 splice site, and deletion types.

Main Results:

• KTS mutations in 46,XX females resulted in isolated NS; in 46,XY individuals, it led to Frasier syndrome.
• Patients with KTS mutations showed older age at presentation and slower progression to CKD stage 5 compared to missense mutations.
• Nonsense mutations presented with WT initially; six patients with missense mutations developed WT after NS diagnosis.

Conclusions:

• KTS mutations are associated with isolated NS in females and Frasier syndrome in phenotypic males, with varying WT risk.
• WT1 mutation analysis is vital for early WT detection and prophylaxis in young NS patients.