title: Linkage analysis and a novel COL4A5 mutation in a large Turkish family with Alport syndrome.
abstract: BACKGROUND
  Alport syndrome (AS) is a renal disease that is characterized by proteinuria and progressive renal failure, and often accompanied by sensorineural hearing loss and ocular changes. Mutations in the genes encoding for three members of the type IV collagen protein family have been found to be the cause of the disease. We describe a large Turkish family with X-linked AS. We performed linkage analysis in this family and sequencing to identify the mutation in the proband whose disease was confirmed by renal biopsy.
  
  
  METHODS
  After genomic DNAs extracted, linkage to the COL4A5 locus was examined using the 2B6 and 2B20, DXS1106, DXS1105 and COL4A5 markers. In addition, COL4A5 gene sequence analysis was performed in the proband.
  
  
  RESULTS
  Genetic linkage analysis demonstrated co-segregation of the disease. Haplotype analysis showed that the same haplotype was carried by all affected males and obligatory carrier females. Mutation analysis of the proband has revealed a novel nonsense mutation (c.1135C>T; Gln379X) in exon 19 of the COL4A5 gene which may lead to a more severe phenotype in affected family members carrying this mutation. According to GenBank data base, this mutation has not been reported previously.
  
  
  CONCLUSIONS
  Genetic testing identified a previously undescribed COL4A5 mutation as the cause of the disease.
authors.affiliation: Department of Medical Genetics, Abant Izzet Baysal University Izzet Baysal Medical School, Bolu-Turkey. esratug@hotmail.com
authors.forename: E
authors.initials: E
authors.lastname: Tug
authors.forename: F E
authors.initials: FE
authors.lastname: Percin
authors.forename: E
authors.initials: E
authors.lastname: Pala
authors.forename: G
authors.initials: G
authors.lastname: Baysoy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018389:Codon, Nonsense; D024141:Collagen Type IV / Q000235:genetics*; D005190:Family; D005260:Female; D008040:Genetic Linkage; D023281:Genomics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000235:genetics*; D014421:Turkey; D055815:Young Adult
chemical_list: C478159:COL4A5 protein, human; D018389:Codon, Nonsense; D024141:Collagen Type IV