Anillin Actin Binding Protein (ANLN) Mutation Associated with C3 Glomerulonephritis – Two Rare Cases

Background:C3 glomerulonephritis (C3GN) is a rare glomerular disease caused by alternative complement pathway dysregulation.ANLN gene mutations have been previously associated with podocytopathies but not linked to C3GN. Case Presentation:We describe two unrelated patients presenting with nephrotic-range proteinuria, low serum C3, and renal biopsy findings consistent with C3GN.Comprehensive workup excluded autoimmune and infectious causes; anti-factor H antibody and serum protein electrophoresis were negative.Genetic testing using whole exome sequencing and MLPA revealed a heterozygous missense variant (p.Asp556Asn) in exon 10 of the ANLN gene (chr7:g.36419276G>A,depth 79x).Treatment with angiotensin converting enzyme inhibitors, mycophenolate mofetil (1 g/day), and corticosteroids (0.5 mg/kg/day tapered over 6 months) resulted in marked proteinuria reduction (Case 1: from 5 g/day to 1.2 g/day in 3 months; Case 2: from 7.5 g/day to 900 mg/day in 6 months) with stable kidney function. Conclusions:These cases represent the first report linking ANLN mutation to C3GN, expanding the phenotypic spectrum of ANLN-associated nephropathies into complement-mediated glomerular disease.The findings highlight the importance of genetic testing in atypical C3GN and underscore implications for diagnosis, management, and counselling.