Inverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis.

Hdl Handle:
http://hdl.handle.net/10147/230473
Title:
Inverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis.
Authors:
Gbadegesin, Rasheed A; Lavin, Peter J; Hall, Gentzon; Bartkowiak, Bartlomiej; Homstad, Alison; Jiang, Ruiji; Wu, Guanghong; Byrd, Alison; Lynn, Kelvin; Wolfish, Norman; Ottati, Carolina; Stevens, Paul; Howell, David; Conlon, Peter; Winn, Michelle P
Affiliation:
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. michelle.winn@duke.edu
Citation:
Inverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis. 2012, 81 (1):94-9 Kidney Int.
Journal:
Kidney international
Issue Date:
Jan-2012
URI:
http://hdl.handle.net/10147/230473
DOI:
10.1038/ki.2011.297
PubMed ID:
21866090
Abstract:
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.
Item Type:
Article
Language:
en
MeSH:
Adolescent; Adult; Aged; Amino Acid Sequence; Amino Acid Substitution; Child; Child, Preschool; Exons; Female; Genes, Dominant; Genes, Recessive; Genetic Testing; Glomerulosclerosis, Focal Segmental; Humans; Infant; Male; Microfilament Proteins; Middle Aged; Models, Molecular; Molecular Sequence Data; Mutant Proteins; Mutation; Mutation, Missense; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Young Adult
ISSN:
1523-1755

Full metadata record

DC FieldValue Language
dc.contributor.authorGbadegesin, Rasheed Aen_GB
dc.contributor.authorLavin, Peter Jen_GB
dc.contributor.authorHall, Gentzonen_GB
dc.contributor.authorBartkowiak, Bartlomiejen_GB
dc.contributor.authorHomstad, Alisonen_GB
dc.contributor.authorJiang, Ruijien_GB
dc.contributor.authorWu, Guanghongen_GB
dc.contributor.authorByrd, Alisonen_GB
dc.contributor.authorLynn, Kelvinen_GB
dc.contributor.authorWolfish, Normanen_GB
dc.contributor.authorOttati, Carolinaen_GB
dc.contributor.authorStevens, Paulen_GB
dc.contributor.authorHowell, Daviden_GB
dc.contributor.authorConlon, Peteren_GB
dc.contributor.authorWinn, Michelle Pen_GB
dc.date.accessioned2012-06-25T11:36:05Z-
dc.date.available2012-06-25T11:36:05Z-
dc.date.issued2012-01-
dc.identifier.citationInverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis. 2012, 81 (1):94-9 Kidney Int.en_GB
dc.identifier.issn1523-1755-
dc.identifier.pmid21866090-
dc.identifier.doi10.1038/ki.2011.297-
dc.identifier.urihttp://hdl.handle.net/10147/230473-
dc.description.abstractFocal 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Kidney internationalen_GB
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAmino Acid Substitution-
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshExons-
dc.subject.meshFemale-
dc.subject.meshGenes, Dominant-
dc.subject.meshGenes, Recessive-
dc.subject.meshGenetic Testing-
dc.subject.meshGlomerulosclerosis, Focal Segmental-
dc.subject.meshHumans-
dc.subject.meshInfant-
dc.subject.meshMale-
dc.subject.meshMicrofilament Proteins-
dc.subject.meshMiddle Aged-
dc.subject.meshModels, Molecular-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMutant Proteins-
dc.subject.meshMutation-
dc.subject.meshMutation, Missense-
dc.subject.meshProtein Structure, Tertiary-
dc.subject.meshSequence Homology, Amino Acid-
dc.subject.meshYoung Adult-
dc.titleInverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. michelle.winn@duke.eduen_GB
dc.identifier.journalKidney internationalen_GB
dc.description.provinceLeinsteren

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