Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis
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Open Access
- 20 December 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 42 (1), 72-76
- https://doi.org/10.1038/ng.505
Abstract
Martin Pollak and colleagues show that missense mutations in the diaphanous inhibitory domain of INF2 cause focal segmental glomerular sclerosis. INF2 encodes a member of the formin family of actin-regulating proteins, highlighting an important role for actin dynamics in podocyte function. 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.Keywords
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