TY - JOUR
T1 - Patients with ACTN4 mutations demonstrate distinctive features of glomerular injury
AU - Henderson, Joel M.
AU - Alexander, Mariam P.
AU - Pollak, Martin R.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2008060613
DO - 10.1681/ASN.2008060613
M3 - Article
C2 - 19357256
AN - SCOPUS:65649096251
SN - 1046-6673
VL - 20
SP - 961
EP - 968
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 5
ER -