Keratoconus is Not Associated With Mutations in COL8A1 and COL8A2

Abstract

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. DNA extraction, polymerase chain reaction amplification, and sequencing of COL8A1 and COL8A2 were performed in 50 unrelated keratoconus and 2 unrelated keratoglobus patients. 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. 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.