title: A two-tier approach to mutation detection in the COL4A5 gene for Alport syndrome.
abstract: About 85% of Alport syndrome is an X-linked semi-dominant condition caused by mutations in the collagen gene, COL4A5. The large size and high GC content of this gene have presented diagnostic laboratories with problems in identifying mutations with greater than about a 50% success rate since the gene was first cloned 16 years ago. An RNA based approach is adopted here for a first pass mutation scanning coupled with more traditional exon-by-exon screening to increase the rate of mutation identification. Twenty-one mutations were identified in twenty-five patients with clear Alport syndrome including four gross deletions, two deep intronic mutations, three frameshifts, three splice site mutations, eight missense mutations and one inframe deletion.
authors.affiliation: Department of Medical & Molecular Genetics, King's College School of Medicine, King's College London, London, United Kingdom.
authors.forename: Kathy
authors.initials: K
authors.lastname: King
authors.forename: Frances A
authors.initials: FA
authors.lastname: Flinter
authors.forename: Peter M
authors.initials: PM
authors.lastname: Green
mesh_terms: D001483:Base Sequence; D024141:Collagen Type IV / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion / Q000235:genetics
chemical_list: C478159:COL4A5 protein, human; D024141:Collagen Type IV