title: A new locus for familial FSGS on chromosome 2p.
abstract: FSGS is a clinicopathologic entity characterized by nephrotic syndrome and progression to ESRD. Although the pathogenesis is unknown, the podocyte seems to play a central role in this disorder. Here, we present six kindreds with hereditary FSGS that did not associate with mutations in known causal genes, and we report a new locus for the disease on chromosome 2p15 in one kindred. We performed genome-wide linkage analysis and refined the linkage area with microsatellite markers and haplotype analysis to define the minimal candidate region. Genome-wide linkage analysis yielded a maximum two-point logarithm of odds (LOD) score of 3.6 for the six families on chromosome 2p. One family contributed the largest proportion of the additive score (LOD 2.02) at this locus. Multipoint parametric LOD score calculation in this family yielded a significant LOD score of 3.1 at markers D2S393 and D2S337, and fine mapping of this region with microsatellite markers defined a minimal candidate region of 0.9 Mb with observed recombinations at markers D2S2332 and RS1919481. We excluded the remaining five families from linkage to this region by haplotype analysis. These data support a new gene locus for familial FSGS on chromosome 2p15. Identification of the mutated gene at this locus may provide further insight into the disease mechanisms of FSGS.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. rasheed.gbadegesin@duke.edu
authors.forename: Rasheed
authors.initials: R
authors.lastname: Gbadegesin
authors.forename: Peter
authors.initials: P
authors.lastname: Lavin
authors.forename: Louis
authors.initials: L
authors.lastname: Janssens
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Bartkowiak
authors.forename: Alison
authors.initials: A
authors.lastname: Homstad
authors.forename: Guanghong
authors.initials: G
authors.lastname: Wu
authors.forename: Brandy
authors.initials: B
authors.lastname: Bowling
authors.forename: Jason
authors.initials: J
authors.lastname: Eckel
authors.forename: Chris
authors.initials: C
authors.lastname: Potocky
authors.forename: Diana
authors.initials: D
authors.lastname: Abbott
authors.forename: Peter
authors.initials: P
authors.lastname: Conlon
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: David
authors.initials: D
authors.lastname: Howell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hauser
authors.forename: Michelle P
authors.initials: MP
authors.lastname: Winn
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002877:Chromosomes, Human / Q000235:genetics; D018450:Disease Progression; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000235:genetics*; D008126:Lod Score; D008297:Male; D009404:Nephrotic Syndrome / Q000150:complications* / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult