title: Identification of four novel mutations in the COL4A5 gene of patients with Alport syndrome.
abstract: The type IV collagen alpha 5 chain (COL4A5) genes of patients with Alport syndrome were tested for major gene rearrangements by Southern blot analysis, using COL4A5 cDNA clones as probes. In addition, individual exons were screened for small mutations by single-strand conformation polymorphism (SSCP) analysis. Four new COL4A5 mutations were detected. A duplication of the nine most 3' located nucleotides of exon 49 and the first nucleotide of intron 49 was identified in the COL4A5 gene of one patient. Two patients displayed single base substitutions leading to, respectively, a proline to threonine and an arginine to glutamine substitution in the C-terminal end. Both substitutions involve amino acids conserved through evolution. In COL4A5 intron 41 a mutation changing the splice acceptor site from AG to AA was identified. All mutations cosegregate with the clinical phenotype of Alport syndrome in affected family members. In a control population of 50 individuals tested by PCR-SSCP these mutations were never identified. Together with two mutations reported previously, a total of six mutations were found in 26 patients with Alport syndrome (23%) after systematic screening of about 30% of the COL4A5 coding region. The clinical features of these six patients are described in detail.
authors.affiliation: Department of Pediatrics, University of Hospital Nijmegen, The Netherlands.
authors.forename: H H
authors.initials: HH
authors.lastname: Lemmink
authors.forename: C H
authors.initials: CH
authors.lastname: Schröder
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: M R
authors.initials: MR
authors.lastname: Nelen
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: K
authors.initials: K
authors.lastname: Tryggvason
authors.forename: W A
authors.initials: WA
authors.lastname: Haagsma-Schouten
authors.forename: A P
authors.initials: AP
authors.lastname: Roodvoets
authors.forename: W
authors.initials: W
authors.lastname: Rascher
authors.forename: B A
authors.initials: BA
authors.lastname: van Oost
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003094:Collagen / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009394:Nephritis, Hereditary / Q000235:genetics*; D009838:Oligodeoxyribonucleotides; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012016:Reference Values; D017386:Sequence Homology, Amino Acid
chemical_list: D009838:Oligodeoxyribonucleotides; D003094:Collagen