ArticleJournal of cataract and refractive surgery2026
Genetic variants in genes regulating lens epithelial cell homeostasis in dead bag syndrome: part 2.
Article in Journal of cataract and refractive surgery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeTo investigate genetic variants associated with the dysregulation of lens epithelial cell (LEC) homeostasis in patients with dead bag syndrome (DBS).
settingCataract and IOL Research Centre, Gujarat, India.
designLaboratory study.
methodsGenomic DNAs from 37 cases and 33 controls were subjected to whole-exome sequencing. Exome-wide rare variant association by the chi-square test followed by gene-wide cumulative rare variant burden analysis using the optimal unified sequence kernel association test was performed. The effect size and the directionality of the genetic variants associated with DBS were assessed by logistic regression analysis.
results12 genes showed a significant ( P < .05) and positive (odds ratio [OR] >1.0) association with DBS of which 9 ( APC2 , CD320 , GEMIN4 , MSLN , TJP1 , TNS1 , TRPM5 , USPL1 , and ZFHX3 ) were expressed in LECs, involving 3 key pathways crucial for LEC homeostasis. Notably, 97.3% (36/37) of cases, vs 54.5% (18/33) of controls, harbored at least 1 variant in these 9 genes. In addition, 83.8% (31/37) of cases had variants in ≥2 genes compared with only 6.1% (2/33) of controls, suggesting an increased risk for DBS in those with multiple affected genes (OR 80.1; 95% CI, 15.0-428.0; P < .0001).
conclusionsThis study highlights a set of rare genetic variants affecting genes involved in RNA processing ( GEMIN4 , USPL1 ), epithelial integrity ( TJP1 , MSLN ), and metabolic homeostasis ( APC2 , CD320 , TNS1 , TRPM5 , ZFHX3 )-3 key pathways crucial for LEC homeostasis. It further supports a multigenic risk model and highlights the potential use of these genes as predictive markers for DBS manifestation.
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