OPTC – OPTN-related Open Angle Glaucoma

The gene OPTC (HGNC:8158) has been recently evaluated for its potential association with OPTN-related open angle glaucoma (MONDO_0100553). In a targeted study of patients with primary open-angle glaucoma (POAG), OPTC was examined alongside a panel of candidate genes, and a rare variant was identified in a subset of cases (PMID:17359525). The overall study screened 200 POAG patients by PCR-based methods and sequencing approaches, aiming to uncover genetic contributors to the complex disease. Although the cohort was moderately sized, only a few patients were found to harbor alterations in OPTC, drawing attention to its candidacy yet necessitating further validation.

The genetic evidence centers on a reported silent variant, designated as c.602 C>T (p.Phe162Phe), which was observed in 3 unrelated POAG patients (PMID:17359525). No additional segregation data or identification of affected relatives was provided. The rarity of this variant in cases compared to its absence in 100 controls supports—but does not definitively prove—a role in disease susceptibility. This limited genetic dataset underscores the need for additional independent studies to strengthen the gene‑disease correlation.

In terms of inheritance mode, the current evidence is most consistent with an autosomal dominant pattern, although definitive familial segregation could not be established. In complex diseases such as open angle glaucoma, genetic variants may contribute in a non‑Mendelian fashion, yet the sporadic discovery of the OPTC alteration hints at a dominant or multifactorial inheritance scheme. The lack of comprehensive family data represents a gap that future studies should address to clarify the genetic architecture underlying OPTC‑associated glaucoma.

Functional studies provide further insight into the biological impact of the variant. Detailed in vitro analyses, including quantitative RT‑PCR and western blot experiments, demonstrated that the silent change causes a significant decrease in both mRNA and protein levels of OPTC (PMID:17359525). These findings support a loss‑of‑function mechanism that may contribute to disease pathogenesis. The experimental evidence is therefore moderately supportive since it directly links the variant to reduced gene expression, despite the variant not altering the amino acid sequence.

While the genetic findings are limited by the small number of affected individuals and the absence of segregation data, the concordant functional data bolsters the hypothesis that OPTC variants may play a role in glaucoma pathogenesis. No conflicting studies have been reported, yet the overall evidence remains preliminary. This scenario highlights the importance of integrating both genetic discoveries and functional analyses in the evaluation of potential disease genes.

In summary, the association between OPTC and OPTN‑related open angle glaucoma is supported by limited genetic evidence—namely the detection of the silent variant c.602 C>T (p.Phe162Phe) in a small subset of patients—and by moderate functional evidence that indicates decreased gene expression. This integrated body of evidence, while still preliminary, suggests that OPTC is a promising candidate for enhancing early diagnostic efforts and could eventually contribute to improved clinical management of POAG.

References

• BMC Molecular Biology • 2007 • Evaluation of the OPTC gene in primary open angle glaucoma: functional significance of a silent change PMID:17359525
• Unspecified Journal • n.d. • Primary open-angle glaucoma candidate gene analysis PMID:38241218

Evidence Based Scoring (AI generated)