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S.A. Hagstrom1, G.T. Pauer1, L.Kleihenz2, K.Zhang1.
1Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH;
2Hathaway Brown School, Shaker Heights, OH.
Purpose: Fuchs' endothelial dystrophy of the cornea (FECD) is a primary disorder of the corneal endothelium and is one of the most common indications of corneal transplantation performed in developed countries. The COL8A2 gene encodes the 2 chain of type VIII collagen and is a major component of endothelial basement membranes, including human corneal Descemet's membrane. Recently, missense mutations in the gene have been identified in patients with FECD. Type VIII collagen is comprised of two chains, 1 and 2, that exist in vivo as hetero-or homotrimers. These findings prompted us to investigate the COL8A1 gene that encodes the 1 chain of type VIII collagen on chromosome 3q11 as a candidate gene for FECD.
Methods: To date, a partial screen of the two coding exons (10 of 23 DNA fragments) for mutations in the proband of 21 unrelated families with autosomal dominant FECD have been performed using SSCP. Variant bands detected by SSCP were further analyzed by direct genomic sequencing.
Results: One heterozygous variant band has been detected in one patient in exon 2. This exon corresponds to the triple helix domain of the protein and it is within this domain where mutations have been identified in COL8A2 in patients with FECD.
Conclusion: To date, we have not found a pathogenic sequence alteration in the COL8A1 gene in patients with FECD. We are proceeding with sequence analysis of the DNA fragment corresponding to the variant band detected in exon 2 and an evaluation of the remaining DNA fragments from both exons in these patients.
Commercial Relationship: S.A. Hagstrom, None; G.T. Pauer, None; L. Kleihenz, None; K. Zhang, None. Grant Identification: Cole Eye Institute, Heed Ophthalmic Foundation, Kirchgessner Foundation
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