Exclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS.

Hdl Handle:
http://hdl.handle.net/10147/253997
Title:
Exclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS.
Authors:
Gbadegesin, Rasheed; Bartkowiak, Bartlomiej; Lavin, Peter J; Mukerji, Nirvan; Wu, Guanghong; Bowling, Brandy; Eckel, Jason; Damodaran, Tirupapuliyur; Winn, Michelle P
Affiliation:
Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, USA. rasheed.gbadegesin@duke.edu
Citation:
Exclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS. 2009, 24 (2):281-5 Pediatr. Nephrol.
Publisher:
Pediatric nephrology (Berlin, Germany)
Journal:
Pediatric nephrology (Berlin, Germany)
Issue Date:
Feb-2009
URI:
http://hdl.handle.net/10147/253997
DOI:
10.1007/s00467-008-1025-5
PubMed ID:
18975016
Abstract:
Focal and segmental glomerulosclerosis (FSGS) is the most common glomerular cause of end-stage kidney disease (ESKD). Although the etiology of FSGS has not been fully elucidated, recent results from the positional cloning of genes mutated in nephrotic syndromes are now beginning to provide insight into the pathogenesis of these diseases. Mutations in PLCE1/NPHS3 have recently been reported as a cause of nephrotic syndrome characterized by diffuse mesangial sclerosis (DMS) histology. One single family with a missense mutation had late onset of the disease that was characterized by FSGS. To further define the role of PLCE1 mutations in the etiology of FSGS, we performed mutational analysis in 69 families with FSGS. A total of 69 families with 231 affected individuals were examined. The median age of disease onset was 26 years (range 1-66 years). Onset of ESKD was at a median age of 35.5 years. Seven variants leading to non-synonymous changes were found, of which only two are new variants (exon 4 c.1682 G>A R561Q, exon 31 c.6518A>G K2173R). No known disease-causing mutations were identified in the families screened. PLCE1/NPHS3 mutations are not a cause of FSGS in this cohort. The absence of mutations in PLCE1/NPHS3 in this study indicates that there are additional genetic causes of FSGS and that hereditary FSGS is a heterogeneous disease. Kindreds appropriate for genome-wide screening are currently being subjected to analysis with the aim of identifying other genetic causes of FSGS.
Item Type:
Article
Language:
en
MeSH:
Adolescent; Adult; Age of Onset; Cohort Studies; Family Health; Glomerulosclerosis, Focal Segmental; Homozygote; Humans; Middle Aged; Mutation, Missense; Phosphoinositide Phospholipase C; Polymorphism, Single Nucleotide; Young Adult
ISSN:
0931-041X

Full metadata record

DC FieldValue Language
dc.contributor.authorGbadegesin, Rasheeden_GB
dc.contributor.authorBartkowiak, Bartlomiejen_GB
dc.contributor.authorLavin, Peter Jen_GB
dc.contributor.authorMukerji, Nirvanen_GB
dc.contributor.authorWu, Guanghongen_GB
dc.contributor.authorBowling, Brandyen_GB
dc.contributor.authorEckel, Jasonen_GB
dc.contributor.authorDamodaran, Tirupapuliyuren_GB
dc.contributor.authorWinn, Michelle Pen_GB
dc.date.accessioned2012-11-29T14:44:19Z-
dc.date.available2012-11-29T14:44:19Z-
dc.date.issued2009-02-
dc.identifier.citationExclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS. 2009, 24 (2):281-5 Pediatr. Nephrol.en_GB
dc.identifier.issn0931-041X-
dc.identifier.pmid18975016-
dc.identifier.doi10.1007/s00467-008-1025-5-
dc.identifier.urihttp://hdl.handle.net/10147/253997-
dc.description.abstractFocal and segmental glomerulosclerosis (FSGS) is the most common glomerular cause of end-stage kidney disease (ESKD). Although the etiology of FSGS has not been fully elucidated, recent results from the positional cloning of genes mutated in nephrotic syndromes are now beginning to provide insight into the pathogenesis of these diseases. Mutations in PLCE1/NPHS3 have recently been reported as a cause of nephrotic syndrome characterized by diffuse mesangial sclerosis (DMS) histology. One single family with a missense mutation had late onset of the disease that was characterized by FSGS. To further define the role of PLCE1 mutations in the etiology of FSGS, we performed mutational analysis in 69 families with FSGS. A total of 69 families with 231 affected individuals were examined. The median age of disease onset was 26 years (range 1-66 years). Onset of ESKD was at a median age of 35.5 years. Seven variants leading to non-synonymous changes were found, of which only two are new variants (exon 4 c.1682 G>A R561Q, exon 31 c.6518A>G K2173R). No known disease-causing mutations were identified in the families screened. PLCE1/NPHS3 mutations are not a cause of FSGS in this cohort. The absence of mutations in PLCE1/NPHS3 in this study indicates that there are additional genetic causes of FSGS and that hereditary FSGS is a heterogeneous disease. Kindreds appropriate for genome-wide screening are currently being subjected to analysis with the aim of identifying other genetic causes of FSGS.en_GB
dc.language.isoenen
dc.publisherPediatric nephrology (Berlin, Germany)en_GB
dc.rightsArchived with thanks to Pediatric nephrology (Berlin, Germany)en_GB
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAge of Onset-
dc.subject.meshCohort Studies-
dc.subject.meshFamily Health-
dc.subject.meshGlomerulosclerosis, Focal Segmental-
dc.subject.meshHomozygote-
dc.subject.meshHumans-
dc.subject.meshMiddle Aged-
dc.subject.meshMutation, Missense-
dc.subject.meshPhosphoinositide Phospholipase C-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshYoung Adult-
dc.titleExclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Pediatrics, Duke University Medical Center, Durham, NC, 27710, USA. rasheed.gbadegesin@duke.eduen_GB
dc.identifier.journalPediatric nephrology (Berlin, Germany)en_GB
dc.description.provinceLeinsteren

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