ABSTRACT
Mutations of ACTN4 cause an autosomal dominant form of focal segmental glomerulosclerosis (FSGS). Presentation usually occurs in the teenage years or later with symptoms of mild proteinuria and slowly progressive renal dysfunction leading to end-stage renal disease (ESRD). We report a 5-year-old female patient who was diagnosed with nephrotic syndrome and did not respond to 6 weeks of oral glucocorticoid therapy. Renal biopsy showed a collapsing variant of FSGS and genetic studies revealed a heterozygous disease-causing mutation in the ACTN4 gene (c.784C>T, p.Ser262Phe). No mutations were found in the NPHS2, TRPC6, and INF2 genes, nor did her parents have any mutations for FSGS. She developed ESRD 6 months after presentation. Although a disease-causing ACTN4 mutation was identified, the contribution of additional polymorphisms in other genes is not known. Such additional polymorphisms may represent yet unidentified epigenetic factors that contributed to the aggressive nature of this child's disease progression. A literature review has revealed only two similar case reports.
