Molecular Genetics Solves the Conundrum of Two Brothers Affected With Proteinuria Coming With a Very Different...

Genetic testing is increasingly used to diagnose kidney diseases, proving cost-effective when performed on selected patients. We present the case of 2 brothers with proteinuria from a young age; one developed kidney insufficiency while the other maintained normal kidney function into late life. This case report investigates whether they inherited the same disease. The proband exhibited focal segmental glomerulosclerosis, with kidney function declining over time. Genetic analysis revealed heterozygous variants in MYH9 and WT1. The MYH9 variant was deemed nonpathogenic, whereas the WT1 variant, associated with autosomal dominant nonsyndromic focal segmental glomerulosclerosis, likely contributed to the proband's kidney insufficiency. However, this variant was absent in his brother, who also had proteinuria but preserved kidney function. Further analysis identified biallelic variants in CUBN in both brothers, suggesting a distinct cause of proteinuria for the brother with normal kidney function. This case illustrates 2 different genetic causes of proteinuria in siblings, highlighting the significance of genetic testing in differential diagnosis and personalized treatment. The findings emphasize the potential misdirection toward glomerular diseases of patients bearing CUBN variants and the general good prognosis associated with them. This case underscores the era of personalized medicine, in which genetic insights tailor treatment strategies for individual patients.