Corneal Perforation After Corneal Cross-Linking in Keratoconus Associated With Potentially Pathogenic ZNF469 Mutations. Issue 8 (August 2019)

• Record Type: Journal Article
• Authors: Zhang, Wenlin; Margines, J. Ben; Jacobs, Deborah S.; Rabinowitz, Yaron S.; Hanser, Evelyn Maryam; Chauhan, Tulika; Chung, Doug; Bykhovskaya, Yelena; Gaster, Ronald N.; Aldave, Anthony J.
• Is Part Of: Cornea. Volume 38:Issue 8(2019)
• Publication Date: 2019-08
• Subjects: keratoconus -- corneal ectasia -- collagen cross-linking -- perforation -- ZNF469; Cornea -- Periodicals; Cornea -- Periodicals; Cornée -- Périodiques; 617.719
• DOI: 10.1097/ICO.0000000000002002
• Languages: English
• ISSNs: 0277-3740

Abstract

Abstract : Purpose: To report a case of bilateral and repetitive corneal perforations after corneal cross-linking (CXL) for keratoconus in a woman harboring potentially pathogenic variants in the ZNF469 gene and to characterize the keratoconus phenotype in this woman and her daughter who shared the same ZNF469 mutations. Methods: Clinical characterization of the proband and her daughter followed by sequencing of the genes associated with brittle cornea syndrome, ZNF469 and PRDM5, in both individuals. Results: An Ashkenazi Jewish woman in her sixth decade presented with diffuse corneal thinning and progressive steepening consistent with keratoconus. After CXL, epithelium-off in the first eye and epithelium-on in the second, she developed spontaneous corneal perforations in each eye. Her daughter in her fourth decade demonstrated a similar pattern of diffuse corneal thinning and progressive corneal steepening but did not undergo CXL and did not develop corneal perforation. Screening of the ZNF469 and PRDM5 genes revealed 3 missense ZNF469 variants (c.2035G>A, c.10244G>C, and c.11119A>G) in cis arrangement on 1 allele of ZNF469 in both proband and her daughter. Although the 3 variants share low (<0.01) global minor allele frequencies, each has significantly higher minor allele frequencies (0.01–0.03) in the Ashkenazi Jewish population, leading to uncertainty regarding a pathogenic role for the identified variants. Conclusions: CXL may be associated with the development of corneal perforation in particular at-risk individuals with keratoconus. Identifying clinical and genetic risk factors, including screening of ZNF469 and PRDM5, may be useful in the prevention of significant complications after CXL. Abstract : Supplemental Digital Content is Available in the Text.