No Pathogenic Mutations Identified in the COL8A2 Gene or Four Positional Candidate Genes in Patients With Posterior Polymorphous Corneal Dystrophy

Abstract

Abstract: : Purpose:To identify the genetic basis of posterior polymorphous corneal dystrophy (PPCD) through screening of the COL8A2 gene, in which a presumed pathogenic mutation has previously been identified in affected patients, and in four positional candidate genes. Methods:DNA extraction, PCR amplification and direct sequencing of the COL8A2, BFSP1, CST3, MMP9 and SLPI genes was 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 this was not considered to be pathogenic as it has been previously identified in unaffected control 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 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.

Keywords: degenerations/dystrophies • candidate gene analysis • cornea: endothelium