COL8A2 – Posterior Polymorphous Corneal Dystrophy

Posterior polymorphous corneal dystrophy (PPMD) has been investigated for association with COL8A2 through familial linkage and mutation screening. Early linkage and haplotype analyses in a multi‐generation family (UM:139) excluded COL8A2 as a disease locus, despite autosomal dominant segregation of PPMD phenotypes (PMID:12654361). Subsequent sequencing of COL8A2 in 5 Japanese PPMD probands and 36 controls also found no coding variants (PMID:15175909), and targeted analysis of 14 unrelated PPMD patients detected only the c.1505C>T (p.Thr502Met) variant in two probands, which is present in unaffected individuals and thus considered nonpathogenic (PMID:15851557).

Across these cohorts (20 probands, three studies), no pathogenic COL8A2 variants have been identified, and functional data linking COL8A2 to corneal endothelial metaplasia in PPMD are lacking. Together, this constitutes strong conflicting evidence against COL8A2 as a causal gene for PPMD. Screening of COL8A2 is not indicated for clinical diagnosis of posterior polymorphous corneal dystrophy.

References

• American journal of ophthalmology • 2003 • Clinicopathologic correlation and genetic analysis in a case of posterior polymorphous corneal dystrophy. PMID:12654361
• Japanese journal of ophthalmology • 2004 • Analysis of COL8A2 gene mutation in Japanese patients with Fuchs' endothelial dystrophy and posterior polymorphous dystrophy. PMID:15175909
• Investigative ophthalmology & visual science • 2005 • No pathogenic mutations identified in the COL8A2 gene or four positional candidate genes in patients with posterior polymorphous corneal dystrophy. PMID:15851557

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