title: Glomerulopathy associated with predominant fibronectin deposits: exclusion of the genes for fibronectin, villin and desmin as causative genes.
abstract: Glomerulopathy with predominant fibronectin deposits (GFD) is a newly recognized autosomal dominant renal disease that leads to albuminuria, microscopic hematuria, hypertension, renal tubular acidosis type IV, and end-stage renal disease in the second to fourth decade of life. Light microscopy documents extensive deposits in the subendothelial space, which on electron microscopy consist of non-oriented 12 x 125 nm fibers. Deposits are strongly immunoreactive for antibodies to fibronectin. We examined the hypothesis that a genetic defect in the gene for fibronectin is responsible for the disease. In a 197 member pedigree, 13 relatives developed end-stage renal failure from the disease. In 99 individuals haplotype analysis was performed using 6 microsatellite markers spanning a > 56 cM interval in chromosome region 2q34, where fibronectin, villin, and desmin map in close proximity. Haplotype analysis resulted in exclusion of the whole range of 78 cM covered by the markers examined. This result excludes fibronectin, villin, and desmin from being the causative genes for GFD in this large kindred.
authors.affiliation: University Children's Hospital, Freiburg University, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Hildebrandt
authors.forename: B
authors.initials: B
authors.lastname: Strahm
authors.forename: A
authors.initials: A
authors.lastname: Prochoroff
authors.forename: M
authors.initials: M
authors.lastname: Cybulla
authors.forename: O
authors.initials: O
authors.lastname: Gemperle
authors.forename: R
authors.initials: R
authors.lastname: Krapf
authors.forename: M
authors.initials: M
authors.lastname: Brandis
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003893:Desmin / Q000235:genetics; D005190:Family; D005260:Female; D005353:Fibronectins / Q000032:analysis / Q000235:genetics*; D005500:Follow-Up Studies; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics / Q000473:pathology; D007678:Kidney Glomerulus / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D008854:Microscopy, Electron; D010375:Pedigree; D014463:Ultrasonography
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D003893:Desmin; D005353:Fibronectins; D005819:Genetic Markers; D008840:Microfilament Proteins; C026615:villin