Exclusion of Nine Positional Candidate Genes for Schnyder Crystalline Corneal Dystrophy

Abstract

Abstract: : Purpose: To identify the genetic basis of Schnyder crystalline corneal dystrophy (SCCD) through screening of nine of the thirty–one positional candidate genes in affected patients. Methods: Mutation screening of nine genes (CORT, ENO1, CLSTN1, DFFA, H6PD, KIF1B, PGD, PEX14, and SSB1) that lie within the candidate gene region for SCCD was performed in members of two families affected with SCCD. Results: No presumed pathogenic coding region mutations were identified in affected members in the two families. Sixteen previously described single nucleotide polymorphisms (SNPs), twelve resulting in synonymous substitutions, were identified in seven of the candidate genes in these affected patients. Four previously described SNPs resulting in non–pathogenic missense substitutions were identified: Tyr1087Cys in the KIF1B gene and Asp246Asn in the PGD gene (both identified in the proband of family 2, but not in the proband’s affected daughter); and Pro554Leu and Arg453Gln (identified in an unaffected control) in the H6PD gene. A novel SNP was identified in the H6PD gene, c.754A>C (Asp151Ala) in the proband of family 1, but not in the proband’s affected mother. Conclusions: The exclusion of these nine genes significantly decreases the number of remaining positional candidate genes for SCCD. As the candidate gene region in each SCCD family previously examined with haplotype analysis has been mapped to the same region of chromosome 1, exclusion of these nine positional candidate genes in the families we examined suggests that other genetic factors are involved in SCCD in these and other affected families.

Keywords: degenerations/dystrophies • cornea: stroma and keratocytes • gene screening