Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis

Elizabeth J. Brown, Johannes S. Schlöndorff, Daniel J. Becker, Hiroyasu Tsukaguchi, Andrea L. Uscinski, Henry N. Higgs, Joel M. Henderson, Martin R. Pollak

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Abstract

Focal segmental glomerulosclerosis (FSGS) is a pattern of kidney injury observed either as an idiopathic finding or as a consequence of underlying systemic conditions. Several genes have been identified that, when mutated, lead to inherited FSGS and/or the related nephrotic syndrome. These findings have accelerated the understanding of glomerular podocyte function and disease, motivating our search for additional FSGS genes. Using linkage analysis, we identified a locus for autosomal-dominant FSGS susceptibility on a region of chromosome 14q. By sequencing multiple genes in this region, we detected nine independent nonconservative missense mutations in INF2, which encodes a member of the formin family of actin-regulating proteins. These mutations, all within the diaphanous inhibitory domain of INF2, segregate with FSGS in 11 unrelated families and alter highly conserved amino acid residues. The observation that alterations in this podocyte-expressed formin cause FSGS emphasizes the importance of fine regulation of actin polymerization in podocyte function.

Original languageEnglish (US)
Pages (from-to)72-76
Number of pages5
JournalNature Genetics
Volume42
Issue number1
DOIs
StatePublished - Jan 2010

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Focal Segmental Glomerulosclerosis
Podocytes
Mutation
Genes
Actins
Nephrotic Syndrome
Missense Mutation
Polymerization
Chromosomes
Kidney
Amino Acids
Wounds and Injuries
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Brown, E. J., Schlöndorff, J. S., Becker, D. J., Tsukaguchi, H., Uscinski, A. L., Higgs, H. N., ... Pollak, M. R. (2010). Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. Nature Genetics, 42(1), 72-76. https://doi.org/10.1038/ng.505

Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. / Brown, Elizabeth J.; Schlöndorff, Johannes S.; Becker, Daniel J.; Tsukaguchi, Hiroyasu; Uscinski, Andrea L.; Higgs, Henry N.; Henderson, Joel M.; Pollak, Martin R.

In: Nature Genetics, Vol. 42, No. 1, 01.2010, p. 72-76.

Research output: Contribution to journalArticle

Brown, EJ, Schlöndorff, JS, Becker, DJ, Tsukaguchi, H, Uscinski, AL, Higgs, HN, Henderson, JM & Pollak, MR 2010, 'Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis', Nature Genetics, vol. 42, no. 1, pp. 72-76. https://doi.org/10.1038/ng.505
Brown EJ, Schlöndorff JS, Becker DJ, Tsukaguchi H, Uscinski AL, Higgs HN et al. Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. Nature Genetics. 2010 Jan;42(1):72-76. https://doi.org/10.1038/ng.505
Brown, Elizabeth J. ; Schlöndorff, Johannes S. ; Becker, Daniel J. ; Tsukaguchi, Hiroyasu ; Uscinski, Andrea L. ; Higgs, Henry N. ; Henderson, Joel M. ; Pollak, Martin R. / Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. In: Nature Genetics. 2010 ; Vol. 42, No. 1. pp. 72-76.
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