Unlike other mutations that cause Cornelia de Lange Syndrome, little is known about SMC3 mutations as they only comprise of < 2% of the cases.




  • Create SMC3-CdLS animal models (especially one that mimics the A485del mutation)
  • Characterize the phenotype of a SMC3-CdLS animal model with respect to:
    • Structural or functional abnormalities, including similarities or differences with existing NIPBL-animal models.
    • Whether the causal SMC3 mutant allele behaves as a loss-of-function or gain-of-function allele, and the extent to which SMC3 is a haplosufficient gene. 
    • Molecular pathways that are dys-regulated in SMC3-CdLS  (e.g. transcriptional abnormalities, disruptions of signaling pathways)
  • Investigate therapeutic approaches that can potentially be borrowed and tested from other transcriptomopathies (e.g. gene editing, gene replacement, protein replacement, RNA editing, RNA trans-splicing, etc)
  • Investigate the effects of pharmacological agents  (e.g. HDAC inhibitors, WNT activators, etc) on SMC3-CdLS animals or cells.
  • Identify relevant signals or pathways that could be affected by drugs.
  • Identify cells in which genetic intervention (e.g., gene editing, antisense oligonucleotides, etc.) would need to be carried out to achieve therapeutic benefit.   
  • Use models of SMC3-CdLS for pre-clinical research to test potential pharmacological or genetic interventions (Anti-sense oligos, CRISPR etc)

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to Vihaan and other kids

affected by CdLS