Clinical, in vitro, and in vivo evidence of WAPL as a novel cohesinopathy gene and phenotypic driver of 10q22.3q23.2 genomic disorder - PubMed
14 hours ago
- #genomic disorder
- #cohesinopathy
- #WAPL
- WAPL identified as a novel cohesinopathy gene linked to developmental delay and intellectual disability.
- Clinical evidence suggests WAPL as a phenotypic driver in the 10q22.3q23.2 genomic disorder region.
- Study includes a cohort with damaging WAPL, PDS5A, and PDS5B variants, showing developmental anomalies.
- CRISPR-engineered models (iPSCs and neurons) show significant gene expression overlaps between WAPL haploinsufficiency and 10q deletion.
- Mouse models with reduced Wapl expression exhibit growth deficits, learning/memory issues, and lethality at lower expression levels.
- Findings highlight the dosage sensitivity of human cohesin and its role in genomic disorders.