title: Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome.
abstract: Alport syndrome (AS) is an hereditary disease of basement membranes characterized by progressive renal failure and deafness. Changes in the glomerular basement membrane (GBM) in AS suggest that the type IV collagen matrix, the major structural component of GBM, is disrupted. We recently isolated the genes for two type IV collagens, alpha 3(IV) and alpha 4(IV), that are encoded head-to-head on human chromosome 2. These chains are abundant in normal GBM but are sometimes absent in AS. We screened for mutations in families in which consanguinity suggested autosomal recessive inheritance. Homozygous mutations were found in alpha 3(IV) in two families and in alpha 4(IV) in two others, demonstrating that these chains are important in the structural integrity of the GBM and that there is an autosomal form of AS in addition to the previously-defined X-linked form.
authors.affiliation: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536-0812.
authors.forename: T
authors.initials: T
authors.lastname: Mochizuki
authors.forename: H H
authors.initials: HH
authors.lastname: Lemmink
authors.forename: M
authors.initials: M
authors.lastname: Mariyama
authors.forename: C
authors.initials: C
authors.lastname: Antignac
authors.forename: M C
authors.initials: MC
authors.lastname: Gubler
authors.forename: Y
authors.initials: Y
authors.lastname: Pirson
authors.forename: C
authors.initials: C
authors.lastname: Verellen-Dumoulin
authors.forename: B
authors.initials: B
authors.lastname: Chan
authors.forename: C H
authors.initials: CH
authors.lastname: Schröder
authors.forename: H J
authors.initials: HJ
authors.lastname: Smeets
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002889:Chromosomes, Human, Pair 2; D003094:Collagen / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009394:Nephritis, Hereditary / Q000235:genetics*; D010375:Pedigree
chemical_list: D003094:Collagen