A novel TRPC6 variant (c.131C>T, p.(Pro44Leu)) associated with focal segmental glomerulosclerosis: a case report

Abstract

Background Pathogenic variants in the transient receptor potential cation channel subfamily C member 6 (TRPC6) cause autosomal dominant focal segmental glomerulosclerosis (FSGS). We report a patient with early-onset FSGS carrying a novel TRPC6 variant not previously described. Case presentation A 21-year-old Chinese male presented with proteinuria (3.17g/24h) and mild renal insufficiency (Cr 103 μmol/L). Renal biopsy confirmed FSGS, not otherwise specified (NOS). Genetic testing was initially declined due to cost concerns. He received losartan, dapagliflozin, strict salt restriction, and ambrisentan, achieving proteinuria reduction to 0.7g/24h without immunosuppression. Two years later, genetic testing identified a novel TRPC6 variant: c.131C>T p.(Pro44Leu), extremely rare in public databases and classified as a variant of uncertain significance. Conclusion This is the first report of the TRPC6 p.Pro44Leu variant, expanding the variant spectrum of TRPC6-associated FSGS. The clinical decision to withhold immunosuppression was guided primarily by the patient’s phenotype (young age, sub-nephrotic proteinuria, FSGS-NOS, and no secondary causes); the TRPC6 variant, although classified as a VUS, provided supportive evidence for a genetic etiology and reinforced this management approach. This case demonstrates that genetic testing can guide personalized management in young patients with FSGS, offering a practical framework for avoiding unnecessary treatment-related morbidity. This case also illustrates that cost and psychological barriers can delay genetic diagnosis and highlights the value of early supportive therapy in genetic FSGS.