Patients with ACTN4 mutations demonstrate distinctive features of glomerular injury

Joel M. Henderson, Mariam P. Alexander, Martin R. Pollak

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Mutations in ACTN4, the gene encoding the actin-binding protein α-actinin-4, are a cause of familial FSGS. We examined kidney biopsies from patients with ACTN4 mutations to characterize systematically the histopathology of kidney damage in these patients and to determine whether distinctive morphologic changes are associated with mutations in this gene. The changes observed with light microscopy were typical of FSGS and were morphologically heterogeneous, similar to other inherited podocytopathies. The ultrastructural characteristics, however, were distinctive: Most notably, the presence of cytoplasmic electron-dense aggregates in podocytes. Indirect immunofluorescence using antibodies to a conserved domain of α-actinin-4 (present in both wild-type and mutant proteins) revealed a segmental and irregular granular staining pattern in the capillary walls of preserved glomeruli of ACTN4 mutants, whereas preserved glomeruli of patients with other podocyte diseases retained a global linear staining pattern for α-actinin-4. These characteristics resemble features observed in mouse models of this disease and may aid in the identification of patients and families who harbor ACTN4 mutations.

Original languageEnglish (US)
Pages (from-to)961-968
Number of pages8
JournalJournal of the American Society of Nephrology
Issue number5
StatePublished - May 1 2009


ASJC Scopus subject areas

  • Nephrology

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