title: Keratoconus is not associated with mutations in COL8A1 and COL8A2.
abstract: OBJECTIVE
  To evaluate the suggested role of the COL8A1 and COL8A2 genes in the pathogenesis of the corneal ectatic disorders keratoconus and keratoglobus through mutation screening in affected patients.
  
  
  METHODS
  DNA extraction, polymerase chain reaction amplification, and sequencing of COL8A1 and COL8A2 were performed in 50 unrelated keratoconus and 2 unrelated keratoglobus patients.
  
  
  RESULTS
  No sequence variations were identified in COL8A1 and COL8A2 in the 2 patients with keratoglobus. Screening of COL8A1 in keratoconus patients revealed a previously identified single nucleotide polymorphism (SNP; c.1850C>T; Pro535Pro), in 1 patient. Screening of COL8A2 in keratoconus patients revealed 7 previously described SNPs: c.14G>A (Gly3Arg); c.112G>A (Ala35Ala); c.1012C>G (Leu335Leu); c.1308G>A (Arg434His); c.1492G>A (Gly495Gly); c.1512C>T (Thr502Met); and c.1765C>T (Pro586Pro). Four novel sequence variants were also identified, each in 1 affected patient: c.38_40dupCTG (Leu11dup), also identified in an unaffected relative of the affected proband, c.667G>A (Gly220Gly), c.1588G>A (Pro527Pro), and c.2026C>T (Val673Val). None of the 3 novel synonymous substitutions identified in COL8A2 was predicted to produce a splice acceptor site.
  
  
  CONCLUSIONS
  The absence of pathogenic mutations in COL8A1 and COL8A2 in patients with keratoconus indicates that other genetic factors are involved in the pathogenesis of this corneal ectatic disorder.
authors.affiliation: Jules Stein Eye Institute, University of California, Los Angeles, CA, USA. aldave@jsei.ucla.edu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Aldave
authors.forename: Nirit
authors.initials: N
authors.lastname: Bourla
authors.forename: Vivek S
authors.initials: VS
authors.lastname: Yellore
authors.forename: Sylvia A
authors.initials: SA
authors.lastname: Rayner
authors.forename: M Ali
authors.initials: MA
authors.lastname: Khan
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Salem
authors.forename: Baris
authors.initials: B
authors.lastname: Sonmez
mesh_terms: D000328:Adult; D024102:Collagen Type VIII / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C443712:COL8A2 protein, human; D024102:Collagen Type VIII