Novel DCN Mutation in Armenian Family With Congenital Stromal Corneal Dystrophy

Abstract

Purpose: Congenital stromal corneal dystrophy (CSCD) is a rare congenital, dominantly inherited disorder characterized by diffuse stromal opacification associated with mutations in the decorin gene (DCN). 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 and genetic basis.Methods: An Armenian family with individuals in 4 consecutive generations demonstrated 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 were sequenced. In silico analysis was performed for identified mutation(s). Excised corneal tissue underwent light, electron microscopic, and immunohistochemical evaluation.Results: Affected individuals demonstrated bilateral, diffuse, panstromal corneal opacification. Three of the 6 individuals diagnosed with CSCD underwent genetic analysis; all demonstrated a novel heterozygous frameshift deletion in exon 8 of DCN (p.His317Thrfs*11), predicted to cause a 33 amino acid truncation and to be damaging and disease causing by SIFT and MutationTaster. Light and electron microscopic examination of an excised cornea demonstrated increased corneal thickness, stromal scarring, keratocyte loss, and an irregularity of lamellar collagen spacing and fibril formation. Immunofluorescent examination demonstrated increased DCN immunostaining, predominantly in the widened interlamellar spaces. Conclusions:We report only the sixth pedigree with genetically confirmed CSCD, associated with a novel DCN frameshift mutation. The clinical evaluation, multimodal imaging, and histopathologic assessment in this family with CSCD broaden our understanding of this rare corneal disease.

Long-Term Follow-Up of Pediatric Excimer Laser-Assisted Penetrating Keratoplasty for Congenital Stromal Corneal Dystrophy

“…CSCD is a very rare autosomal dominant inherited corneal dystrophy that has only been described in a few families. To our knowledge, this is the 10th reported 1,6–13 family, the seventh genetically 4,5,9–11,13 confirmed family and the first patient from Greece.…”

“…3,4 The disease is extremely rare because only 9 families have been described in the literature, of which 6 were genetically confirmed. 1,2,[5][6][7][8][9][10][11][12][13] In 2005, Bredrup et al 4 reported a frameshift mutation of the decorin (DCN) gene (c.967delT) on chromosome 12q21 leading to a C-terminal truncated protein. Decorin is a proteoglycan protein containing a single glycosaminoglycan side chain and a core protein consisting of leucine-rich repeats.…”

“…The disease is extremely rare because only 9 families have been described in the literature, of which 6 were genetically confirmed. 1,2,5–13…”

Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant

“…Additionally, SPARCL1 stimulates decorin production (24). DCN is the established genetic cause of CSCD, with reports of cases with premature stop codons (5)(6)(7)(9)(10)(11)(12). Although CSCD typically presents with an onset in childhood, there is at least one report of the onset of the disease in adulthood, in which a novel missense DCN variant was identified (8).…”

“…Most corneal dystrophies are autosomal dominant, although autosomal recessive and X-linked corneal dystrophies have been described; however, the genetic basis for some presumed dystrophies remains unresolved (3). Congenital stromal corneal dystrophy (CSCD) is a rare autosomal dominant corneal dystrophy caused by variants in DCN (5)(6)(7)(8)(9)(10)(11)(12). Here, we describe the clinical features, histopathology, and genetic cause of a novel autosomal dominant stromal corneal dystrophy, which exhibits clinical similarities to CSCD and may share a common molecular mechanism.…”