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Case Western Study Links Inherited VSIG10L Mutations to Barrett’s Esophagus, Debuts Genetics-Based Mouse Model

Defects in VSIG10L leave the esophageal lining vulnerable to bile-driven damage.

Overview

  • Researchers analyzed 684 individuals across 302 families with multiple cases of Barrett’s esophagus or esophageal cancer and found inherited VSIG10L mutations in a subset of affected relatives.
  • Laboratory studies show VSIG10L acts as a quality-control mechanism for esophageal cells, with loss of function impairing maturation and weakening barrier integrity.
  • Genetically engineered mice carrying human-equivalent VSIG10L mutations developed structural and molecular disruption of the esophageal lining and progressed to Barrett’s-like disease after bile-acid exposure.
  • The mouse model is described as the first for Barrett’s esophagus based directly on human genetic predisposition.
  • The peer-reviewed findings were published in Nature Communications, and the team says family members can now be screened for VSIG10L variants to flag higher-risk individuals.