Molecular Characteristics
The DLL1gene encodes a ligand in the Notch signalling pathway, which is essential for regulating cell differentiation, proliferation, and fate determination during embryonic development. DLL1, a human homolog of the Drosophila Delta ligand, plays a critical role in the segmentation clock that governs somite formation—precursors to the vertebral column. Mutations or dysregulation of DLL1 can disrupt Notch signalling, leading to abnormal somite patterning and resulting in congenital vertebral malformations such as spondylocostal dysostosis and other spinal segmentation defects. Proper DLL1 function is therefore vital for normal vertebral development and axial skeletal integrity.
Mutations and Pathophysiology
Barhoumi1 et al. (2019) identified homozygous mutation in DLL1(c.1534G>A; (p.Gly512Arg) in patients with multiple vertebral body anomalies.
Diagnostic Testing
Genetic testing: Whole-exome sequencing (WES) or Whole genome sequencing (WGS).
X-rays and CT Scan: Multiple vertebral body anomalies.
DLL1