Abstract
Purpose :
Congenital stromal corneal dystrophy (CSCD) is a rare congenital, dominantly inherited disorder characterized by diffuse stromal opacification. CSCD is associated with mutations in the decorin gene (DCN), which encodes one of the highly expressed small leucine rich proteoglycans in the extracellular matrix of the corneal stroma. As only 5 families with genetically confirmed CSCD have been reported, the identification of a novel pedigree provides the opportunity to better characterize the phenotype, ultrastructural features, clinical course and underlying genetic basis.
Methods :
We report a novel Armenian family with affected individuals in 4 consecutive generations demonstrating clinical features consistent with CSCD. Consented individuals underwent slit lamp examination, optical coherence tomography and confocal microscopy. Genomic DNA was collected from saliva and all coding and adjacent intronic regions of DCN underwent PCR amplification and Sanger sequencing. In silico analysis was performed for identified mutations. Corneal tissue excised at the time of corneal transplantation underwent immunohistochemical and electron microscopic evaluation.
Results :
Slit lamp examination of affected individuals showed bilateral, diffuse, panstromal corneal opacification. Two of the 6 individuals diagnosed with CSCD based on history and/or examination underwent genetic analysis; both demonstrated a novel heterozygous frameshift deletion in exon 8 of DCN (c.948delA (p.His317Thrfs*11)), predicted to cause a 33 amino acid truncation. The mutation was predicted to be damaging and disease causing by SIFT and Mutation Taster. Electron and light microscopic examination of an excised cornea demonstrated increased corneal thickness, stromal scarring, keratocyte loss and an irregularity of lamellar collagen spacing and fibril formation.
Conclusions :
We report only the sixth affected pedigree with genetically confirmed CSCD, associated with a novel DCN frameshift mutation in an Armenian family. The clinical evaluation, multimodal imaging, and histopathological assessment of this family with CSCD broaden our understanding of the rare corneal disease.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.