title: Sequence variants in COL4A1 and COL4A2 genes in Ecuadorian families with keratoconus.
abstract: OBJECTIVE
  Keratoconus (KTCN) is a non-inflammatory, usually bilateral disorder of the eye which results in the conical shape and the progressive thinning of the cornea. Several studies have suggested that genetic factors play a role in the etiology of the disease. Several loci were previously described as possible candidate regions for familial KTCN; however, no causative mutations in any genes have been identified for any of these loci. The purpose of this study was to evaluate role of the collagen genes collagen type IV, alpha-1 (COL4A1) and collagen type IV, alpha-2 (COL4A2) in KTCN in Ecuadorian families.
  
  
  METHODS
  COL4A1 and COL4A2 in 15 Ecuadorian KTCN families were examined with polymerase chain reaction amplification, and direct sequencing of all exons, promoter and intron-exon junctions was performed.
  
  
  RESULTS
  Screening of COL4A1 and COL4A2 revealed numerous alterations in coding and non-coding regions of both genes. We detected three missense substitutions in COL4A1: c.19G>C (Val7Leu), c.1663A>C (Thr555Pro), and c.4002A>C (Gln1334His). Five non-synonymous variants were identified in COL4A2: c.574G>T (Val192Phe), c.1550G>A (Arg517Lys), c.2048G>C (Gly683Ala), c.2102A>G (Lys701Arg), and c.2152C>T (Pro718Ser). None of the identified sequence variants completely segregated with the affected phenotype. The Gln1334His variant was possibly damaging to protein function and structure.
  
  
  CONCLUSIONS
  This is the first mutation screening of COL4A1 and COL4A2 genes in families with KTCN and linkage to a locus close to these genes. Analysis of COL4A1 and COL4A2 revealed no mutations indicating that other genes are involved in KTCN causation in Ecuadorian families.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Justyna A
authors.initials: JA
authors.lastname: Karolak
authors.forename: Karolina
authors.initials: K
authors.lastname: Kulinska
authors.forename: Dorota M
authors.initials: DM
authors.lastname: Nowak
authors.forename: Jose A
authors.initials: JA
authors.lastname: Pitarque
authors.forename: Andrea
authors.initials: A
authors.lastname: Molinari
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rydzanicz
authors.forename: Bassem A
authors.initials: BA
authors.lastname: Bejjani
authors.forename: Marzena
authors.initials: M
authors.lastname: Gajecka
mesh_terms: D000595:Amino Acid Sequence; D016022:Case-Control Studies; D024141:Collagen Type IV / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D003315:Cornea / Q000473:pathology; D004484:Ecuador; D005260:Female; D020869:Gene Expression Profiling; D006239:Haplotypes; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: C547475:COL4A1 protein, human; C502625:COL4A2 protein, human; D024141:Collagen Type IV