title: A nonsense mutation in the COL4A5 collagen gene in a family with X-linked juvenile Alport syndrome.
abstract: The X-linked form of Alport syndrome is associated with mutations in the COL4A5 gene encoding the alpha 5-chain of type IV collagen. By using PCR-amplification and direct sequencing we identified a novel mutation involving a deletion of the last two bases in the codon GGA for Glycine-1479 in exon 47 of the COL4A5 gene in a patient with a juvenile form of X-linked Alport syndrome with deafness. This two base deletion caused a shift in the reading frame and introduced a premature stop codon which resulted in an alpha 5(IV)-chain shortened by 202 residues and lacking almost the entire NC1 domain. The mutation was found to co-segregate with the disease in the family. The information of the sequence variation in this family was used to perform carrier detection and prenatal diagnosis by allele-specific oligonucleotide hybridization analysis and direct sequencing of PCR amplified exon 47. Prenatal diagnosis on chorionic villi tissue, obtained from one of the female carriers in the family, revealed a male fetus hemizygous for the mutated allele. A subsequent prenatal test in her next pregnancy revealed a normal male fetus. Prenatal diagnosis of Alport syndrome has not previously been reported.
authors.affiliation: Institute of Human Genetics, University of Aarhus, Denmark.
authors.forename: J M
authors.initials: JM
authors.lastname: Hertz
authors.forename: N
authors.initials: N
authors.lastname: Heiskari
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: U B
authors.initials: UB
authors.lastname: Jensen
authors.forename: K
authors.initials: K
authors.lastname: Tryggvason
mesh_terms: D000328:Adult; D001483:Base Sequence; D002872:Chromosome Deletion; D003094:Collagen / Q000235:genetics*; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D005091:Exons; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis*; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005998:Glycine; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009394:Nephritis, Hereditary / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014960:X Chromosome
chemical_list: D017931:DNA Primers; D003094:Collagen; D004247:DNA; D005998:Glycine