Only a minority of abnormal segmentation phenotypes appear to follow Mendelian inheritance but three genes--DLL3, MESP2 and LNFG--have now been identified for spondylocostal dysostosis (SCD), a spinal malformation characterized by extensive hemivertebrae, trunkal shortening and abnormally aligned ribs with points of fusion.
A new mutation in the skeletal ryanodine receptor gene (RYR1) is potentially causative of malignant hyperthermia, central core disease, and severe skeletal malformation.
Novel mutations in DLL3, a somitogenesis gene encoding a ligand for the Notch signalling pathway, cause a consistent pattern of abnormal vertebral segmentation in spondylocostal dysostosis.
Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene Dll3 are associated with disruption of the segmentation clock within the presomitic mesoderm.
In humans, mutations in genes required for oscillation, such as Delta-like 3 (DLL3), result in abnormal segmentation of the vertebral column, as found in spondylocostal dysostosis syndrome, suggesting that the segmentation clock also acts during human embryonic development.