A frameshift variant in FAM129C contributes to achalasia through B cell responses against the GABAA receptor - PubMed
3 hours ago
- #achalasia
- #FAM129C
- #neuroimmunology
- Achalasia is linked to a frameshift variant in FAM129C, identified through trio-based whole-genome sequencing.
- CRISPR/Cas9-engineered Fam129c-mutant mice show achalasia-like symptoms, including higher lower esophageal sphincter pressure and loss of inhibitory neurons.
- Multi-omic analyses reveal B cell expansion and activation in the lower esophageal sphincter, with humoral immune responses implicated.
- B cell accumulation occurs before neuronal loss, and anti-CD20 or intravenous immunoglobulin treatments partially reverse symptoms.
- GABAA receptor is identified as a potential autoantibody target, suggesting a neuroimmune mechanism in achalasia pathogenesis.