DCN – Congenital Stromal Corneal Dystrophy

Congenital stromal corneal dystrophy (CSCD) is an autosomal dominant disorder presenting with diffuse corneal clouding from birth, in the absence of systemic features. Five unrelated pedigrees harbor heterozygous DCN variants, implicating altered decorin function in the pathogenesis.

Inheritance is autosomal dominant. Segregation has been demonstrated in 17 affected relatives across five families (PMID:15671264; PMID:21993463; PMID:22870031; PMID:24413633; PMID:36964172).

Genetic analyses revealed a spectrum of truncating and one missense variant clustering in exon 8 of DCN, which encodes the C-terminal glycosaminoglycan binding domain of decorin. The initial family carried c.967delT (p.Ser323fsTer5) (PMID:15671264), followed by c.947delG (p.Gly316AspfsTer12) (PMID:21993463), c.1036T>G (p.Cys346Gly) (PMID:22870031), c.962delA (p.Lys321ArgfsTer7) (PMID:24413633), and a de novo c.953del (p.Asn318ThrfsTer10) (PMID:36964172).

Functional studies on patient corneal buttons by transmission electron microscopy reveal normal collagen fibril arrays disrupted by abnormal interlamellar fibrils, supporting a dominant-negative mechanism in which truncated decorin perturbs collagen fibrillogenesis (PMID:15671264).

No conflicting genetic or phenotypic evidence has been reported. The consistency of phenotype, segregation across multiple families, and ultrastructural concordance establish a moderate ClinGen-level association for DCN in CSCD.

Key Take-home: Pathogenic DCN truncating variants cause dominant congenital stromal corneal dystrophy by disrupting collagen matrix assembly, supporting inclusion in diagnostic gene panels and enabling accurate genetic counseling.

References

• Investigative ophthalmology & visual science • 2005 • Congenital stromal dystrophy of the cornea caused by a mutation in the decorin gene. PMID:15671264
• Cornea • 2011 • A novel mutation of the decorin gene identified in a Korean family with congenital hereditary stromal dystrophy. PMID:21993463
• Korean journal of ophthalmology : KJO • 2012 • A novel decorin gene mutation in congenital hereditary stromal dystrophy: a Korean family. PMID:22870031
• Cornea • 2014 • Novel decorin mutation in a Chinese family with congenital stromal corneal dystrophy. PMID:24413633
• Human genome variation • 2023 • A pediatric case of congenital stromal corneal dystrophy caused by the novel variant c.953del of the DCN gene. PMID:36964172

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