Keratoconus is not associated with mutations in COL8A1 and COL8A2.
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.
Aldave
Anthony J
AJ
Jules Stein Eye Institute, University of California, Los Angeles, CA, USA. aldave@jsei.ucla.edu
Bourla
Nirit
N
Yellore
Vivek S
VS
Rayner
Sylvia A
SA
Khan
M Ali
MA
Salem
Andrew K
AK
Sonmez
Baris
B
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
C443712:COL8A2 protein, human; D024102:Collagen Type VIII