title: The gene for human fibronectin glomerulopathy maps to 1q32, in the region of the regulation of complement activation gene cluster.
abstract: Fibronectin glomerulopathy (GFND) is a newly recognized autosomal dominant disease of the kidney that results in albuminuria, microscopic hematuria, hypertension, renal tubular acidosis type IV, and end-stage renal disease in the 2d to 6th decade of life. The disease is characterized histologically by massive deposits of fibronectin (Fn) present in the subendothelial spaces of renal glomerular capillaries. The cause of human GFND is unknown. In order to localize a candidate gene for GFND, we performed linkage analysis of a large, 193-member pedigree containing 13 affected individuals. Since we had previously excluded the genes for Fn and uteroglobin as candidate genes for GFND, a total-genome search for linkage was performed. Examination of 306 microsatellite markers resulted in a maximum two-point LOD score of 4.17 at a recombination fraction of. 00 for marker D1S249, and a maximum multipoint LOD score of 4.41 for neighboring marker D1S2782. By detection of recombination events, a critical genetic interval of 4.1 cM was identified, which was flanked by markers D1S2872 and D1S2891. These findings confirm that GFND is a distinct disease entity among the fibrillary glomerulopathies. Gene identification will provide insights into the molecular interactions of Fn in GFND, as well as in genetically unaltered conditions.
authors.affiliation: University Children's Hospital, Freiburg University, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Vollmer
authors.forename: M
authors.initials: M
authors.lastname: Jung
authors.forename: F
authors.initials: F
authors.lastname: Rüschendorf
authors.forename: R
authors.initials: R
authors.lastname: Ruf
authors.forename: T
authors.initials: T
authors.lastname: Wienker
authors.forename: A
authors.initials: A
authors.lastname: Reis
authors.forename: R
authors.initials: R
authors.lastname: Krapf
authors.forename: F
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D000328:Adult; D000367:Age Factors; D002648:Child; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003167:Complement Activation / Q000235:genetics*; D020224:Expressed Sequence Tags; D005260:Female; D005353:Fibronectins / Q000032:analysis*; D005799:Genes, Dominant; D015894:Genome, Human; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000209:etiology; D007678:Kidney Glomerulus; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance; D016324:Sequence Tagged Sites
chemical_list: D005353:Fibronectins