title: A genome search for primary vesicoureteral reflux shows further evidence for genetic heterogeneity.
abstract: Vesicoureteral reflux (VUR) is the most common disease of the urinary tract in children. In order to identify gene(s) involved in this complex disorder, we performed a genome-wide search in a selected sample of 31 patients with primary VUR from eight families originating from southern Italy. Sixteen additional families with 41 patients were included in a second stage. Nonparametric, affected-only linkage analysis identified four genomic areas on chromosomes 1, 3, and 4 (p < 0.05); the best result corresponded to the D3S3681-D3S1569 interval on chromosome 3 (nonparametric linkage score, NPL = 2.75, p = 0.008). This region was then saturated with 26 additional markers, tested in the complete group of 72 patients from 24 families (NPL = 2.01, p = 0.01). We identified a genomic area on 3q22.2-23, where 26 patients from six multiplex families shared overlapping haplotypes. However, we did not find evidence for a common ancestral haplotype. The region on chromosome 1 was delimited to 1p36.2-34.3 (D1S228-D1S255, max. NPL = 1.70, p = 0.03), after additional fine typing. Furthermore, on chromosome 22q11.22-12.3, patients from a single family showed excess allele sharing (NPL = 3.35, p = 0.015). Only the chromosome 3q region has been previously reported in the single genome-wide screening available for primary VUR. Our results suggest the presence of several novel loci for primary VUR, giving further evidence for the genetic heterogeneity of this disorder.
authors.affiliation: Department of Clinical Genetics, Erasmus MC Rotterdam, Rotterdam, The Netherlands.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Conte
authors.forename: Aida M
authors.initials: AM
authors.lastname: Bertoli-Avella
authors.forename: Bianca M
authors.initials: BM
authors.lastname: de Graaf
authors.forename: Francesca
authors.initials: F
authors.lastname: Punzo
authors.forename: Giuliana
authors.initials: G
authors.lastname: Lama
authors.forename: Angela
authors.initials: A
authors.lastname: La Manna
authors.forename: Carolina
authors.initials: C
authors.lastname: Grassia
authors.forename: Pier Francesco
authors.initials: PF
authors.lastname: Rambaldi
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Silverio
authors.initials: S
authors.lastname: Perrotta
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004252:DNA Mutational Analysis; D005190:Family; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D014718:Vesico-Ureteral Reflux / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery
chemical_list: D005819:Genetic Markers