Purpose: The aim of this study was to characterize the congenital stromal corneal dystrophy (CSCD) pathological and clinical phenotype in a Chinese family with a novel mutation of decorin and its possible molecular pathogenesis.
Methods: Molecular genetic analyses were performed on 5 patients with CSCD. Clinical characteristics, optical coherence tomography, and confocal microscopic study were evaluated. The corneal specimens from patients with CSCD were sent for light and electron microscopic evaluation. A protein modeling study was carried out to assess the effect of the mutation on the protein structure.
Results: Sequencing analysis of DCN revealed that all patients with CSCD were heterozygous for a 1-bp deletion at nucleotide 962 (c.962delA) in exon 8. This causes a premature termination of the decorin protein by frameshift, causing the deletion of 33 amino acids in the C-terminal end of the decorin protein. Optical coherence tomography and confocal microscopic study demonstrated that the corneal lamellar structure was disrupted and that this is more severe in the anterior and posterior central stroma. Histopathological study showed that electron-lucent zones were present between the normal-appearing collagen lamellae in the patients with CSCD. Abnormally thinned collagen filaments were identified in the electron-lucent zones, which could be due to abnormal decorin binding to the collagen microfibrils. Protein modeling studies involving wild-type and mutant protein indicated that mutant decorin might be unable to bind to all 4 collagen microfibrils as the normal decorin would.
Conclusions: We present the clinical, histopathological, and molecular genetic assessment of a Chinese family with CSCD in which a novel DCN mutation was identified. Our findings add to the allelic heterogeneity of this rare form of inherited corneal disease.