title: Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome.
abstract: Mutations in either the COL4A3 or the COL4A4 genes, encoding the alpha3 and alpha4 chains of type IV collagen, are responsible for the autosomal-recessive form of Alport syndrome, a progressive hematuric nephropathy characterized by glomerular basement membrane abnormalities. Reported here are the complete COL4A3 exon-intron structure and a comprehensive screen for mutations of the 52 COL4A3 exons in 41 unrelated patients diagnosed as having autosomal Alport syndrome. This resulted in the identification of 21 mutations that are expected to be causative. Furthermore, it is shown that heterozygous COL4A3 missense mutations, when symptomatic, can be associated with a broad range of phenotypes, from familial benign hematuria to the complete features of Alport syndrome nephropathy.
authors.affiliation: INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Heidet
authors.affiliation: INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Arrondel
authors.affiliation: INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Forestier
authors.affiliation: INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Lola
authors.initials: L
authors.lastname: Cohen-Solal
authors.affiliation: INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Mollet
authors.affiliation: INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gutierrez
authors.affiliation: Renal Unit, Paphos General Hospital, Paphos, Cyprus.
authors.forename: Christophoros
authors.initials: C
authors.lastname: Stavrou
authors.affiliation: INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Marie Claire
authors.initials: MC
authors.lastname: Gubler
authors.affiliation: INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
mesh_terms: D001483:Base Sequence; D003094:Collagen / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005260:Female; D006579:Heterozygote; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009394:Nephritis, Hereditary / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D003094:Collagen