title: A novel COL4A3 mutation causes autosomal-recessive Alport syndrome in a large Turkish family.
abstract: BACKGROUND
  Alport syndrome (AS) is a genetically heterogeneous disorder that is characterized by hematuria, progressive renal failure typically resulting in end-stage renal disease, sensorineural hearing loss, and variable ocular abnormalities. Only 15% of cases with AS are autosomal recessive and are caused by mutations in the COL4A3 or COL4A4 genes, encoding type IV collagen.
  
  
  METHODS
  Clinical data in a large consanguineous family with four affected members were reviewed, and genomic DNA was extracted. For mapping, 15 microsatellite markers flanking COL4A3, COL4A4, and COL4A5 in 16 family members were typed. For mutation screening, all coding exons of COL4A3 were polymerase chain reaction- amplified and Sanger-sequenced from genomic DNA.
  
  
  RESULTS
  The disease locus was mapped to chromosome 2q36.3, where COL4A3 and COL4A4 reside. Sanger sequencing revealed a novel mis-sense mutation (c.2T>C; p.M1T) in exon 1 of COL4A3. The identified nucleotide change was not found in 100 healthy ethnicity-matched controls via Sanger sequencing.
  
  
  CONCLUSIONS
  We present a large consanguineous Turkish family with AS that was found to have a COL4A3 mutation as the cause of the disease. Although the relationship between the various genotypes and phenotypes in AS has not been fully elucidated, detailed clinical and molecular analyses are helpful for providing data to be used in genetic counseling. It is important to identify new mutations to clarify their clinical importance, to assess the prognosis of the disease, and to avoid renal biopsy for final diagnosis.
authors.affiliation: Department of Medical Genetics, Erciyes University School of Medicine, Kayseri, Turkey.
authors.forename: Asli Subasioglu
authors.initials: AS
authors.lastname: Uzak
authors.forename: Bulent
authors.initials: B
authors.lastname: Tokgoz
authors.forename: Munis
authors.initials: M
authors.lastname: Dundar
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
mesh_terms: D000328:Adult; D001324:Autoantigens / Q000235:genetics*; D024141:Collagen Type IV / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D009394:Nephritis, Hereditary / Q000235:genetics*; D010375:Pedigree; D014421:Turkey
chemical_list: D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain