title: Detection of mutations in the COL4A5 gene by SSCP in X-linked Alport syndrome.
abstract: Alport syndrome is a progressive renal disease leading to chronic renal failure, which often is accompanied by sensorineural deafness and ophthalmological signs in the form of anterior lenticonus. The X-linked form of the disease is caused by mutations in the COL4A5 gene encoding the alpha5-chain of type IV-collagen. We performed mutation analysis of the COL4A5 gene by PCR-SSCP analysis of each of the 51 exons with flanking intronic sequences in 81 patients suspected of X-linked Alport syndrome including 29 clear X-linked cases, 37 cases from families with a pedigree compatible with X-linked inheritance, and 15 isolated cases. We found a mutation detection rate of 52% (42/81) (58% in males and 21% in females), and 69% (20/29) in families who clearly demonstrated X-linked inheritance. Thirty-six different mutations were found in 42 patients comprising 16 missense mutations, seven frameshifts, three in-frame deletions, four nonsense mutations, and six splice site mutations. Twenty-two of the mutations have not previously been reported. Furthermore, we found one non-pathogenic amino acid substitution, one rare variant in a non-coding region, and one polymorphism with a heterozygosity of 28%. Three de novo mutations were found, two of which were paternal and one of maternal origin.
authors.affiliation: Department of Clinical Genetics, Aarhus University Hospital, Aarhus C, Denmark. hertz@aaa.dk
authors.forename: J M
authors.initials: JM
authors.lastname: Hertz
authors.forename: I
authors.initials: I
authors.lastname: Juncker
authors.forename: U
authors.initials: U
authors.lastname: Persson
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
authors.forename: J
authors.initials: J
authors.lastname: Schmidtke
authors.forename: M B
authors.initials: MB
authors.lastname: Petersen
authors.forename: M
authors.initials: M
authors.lastname: Kjeldsen
authors.forename: N
authors.initials: N
authors.lastname: Gregersen
mesh_terms: D018389:Codon, Nonsense / Q000235:genetics; D024141:Collagen Type IV / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009394:Nephritis, Hereditary / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D022821:RNA Splice Sites / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D014960:X Chromosome / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D024141:Collagen Type IV; D022821:RNA Splice Sites