Purpose: To identify the genetic basis of posterior polymorphous corneal dystrophy (PPCD) through screening of four positional candidate genes and the COL8A2 gene, in which a presumed pathogenic mutation has previously been identified in affected patients.
Methods: DNA extraction, PCR amplification, and direct sequencing of the COL8A2, BFSP1, CST3, MMP9, and SLPI genes were performed in 14 unrelated, affected patients and in unaffected family members.
Results: In the COL8A2 gene, the previously identified, presumed pathogenic mutation (Gln455Lys) was not discovered in any of the affected patients. A missense mutation, Thr502Met, was identified in 2 of the 14 affected probands, although it was not considered to be pathogenic, as it has been identified in unaffected individuals. Although several novel and previously identified single nucleotide polymorphisms producing synonymous and missense amino acid substitutions were identified in the COL8A2, BFSP1, CST3, MMP9, and SLPI genes, no presumed pathogenic sequence variants were found.
Conclusions: No pathogenic mutations were identified in the COL8A2 gene or in several positional candidate genes in a series of patients with PPCD, indicating that other genetic factors are involved in the development of this autosomal dominant corneal dystrophy.