Inverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis.
Journal Article (Journal Article)
Focal and segmental glomerulosclerosis (FSGS) is a major cause of end-stage kidney disease. Recent advances in molecular genetics show that defects in the podocyte play a major role in its pathogenesis and mutations in inverted formin 2 (INF2) cause autosomal dominant FSGS. In order to delineate the role of INF2 mutations in familial and sporadic FSGS, we sought to identify variants in a large cohort of patients with FSGS. A secondary objective was to define an approach for genetic screening in families with autosomal dominant disease. A total of 248 individuals were identified with FSGS, of whom 31 had idiopathic disease. The remaining patients clustered into 64 families encompassing 15 from autosomal recessive and 49 from autosomal dominant kindreds. There were missense mutations in 8 of the 49 families with autosomal dominant disease. Three of the detected variants were novel and all mutations were confined to exon 4 of INF2, a regulatory region responsible for 90% of all changes reported in FSGS due to INF2 mutations. Thus, in our series, INF2 mutations were responsible for 16% of all cases of autosomal dominant FSGS, with these mutations clustered in exon 4. Hence, screening for these mutations may represent a rapid, non-invasive and cost-effective method for the diagnosis of autosomal dominant FSGS.
Full Text
Duke Authors
Cited Authors
- Gbadegesin, RA; Lavin, PJ; Hall, G; Bartkowiak, B; Homstad, A; Jiang, R; Wu, G; Byrd, A; Lynn, K; Wolfish, N; Ottati, C; Stevens, P; Howell, D; Conlon, P; Winn, MP
Published Date
- January 2012
Published In
Volume / Issue
- 81 / 1
Start / End Page
- 94 - 99
PubMed ID
- 21866090
Pubmed Central ID
- PMC3694501
Electronic International Standard Serial Number (EISSN)
- 1523-1755
Digital Object Identifier (DOI)
- 10.1038/ki.2011.297
Language
- eng
Conference Location
- United States