[Clinical and pathological features and mutational types of WT1 mutation-associated nephropathy]

Area of Science:

• Nephrology
• Genetics
• Pathology

Background:

• WT1 mutation-associated nephropathy (WT1MAN) encompasses a spectrum of kidney diseases.
• Understanding the relationship between WT1 mutational types and clinical/pathological manifestations is crucial for diagnosis and management.

Purpose of the Study:

• To investigate the clinical and pathological characteristics of WT1MAN.
• To identify the types of WT1 mutations and their correlation with disease presentation and progression.

Main Methods:

• Retrospective analysis of clinical, pathological, and WT1 mutation data from 20 patients over ten years.
• Categorization of patients into Denys-Drash syndrome (DDS), Frasier syndrome (FS), and isolated nephropathy (IN) based on clinical and genetic findings.

Main Results:

• Missense mutations were the most frequent WT1 variants (11/20).
• Patients with splice mutations exhibited early-onset nephropathy (4/5), rapid progression (4/5), and glomerular basement membrane (GBM) layering (4/4).
• Calcineurin inhibitors (CNIs) demonstrated effectiveness in reducing or eliminating proteinuria in 8/9 WT1MAN patients.

Conclusions:

• WT1MAN shows varied presentations depending on the mutation type.
• Splice mutations are associated with aggressive kidney disease phenotypes.
• CNI treatment offers a promising therapeutic option for managing proteinuria in WT1MAN.