Disease relevance of DLL3

• Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis [1].
• We present the first molecular study of congenital scoliosis by analysis of the candidate gene DLL3 and demonstrate one novel missense variant [2].

High impact information on DLL3

• DLL3 encodes a ligand for the Notch receptor and, when mutated, defective somitogenesis occurs resulting in a consistent and distinctive pattern of AVS affecting the entire spine [3].
• Within this group, the radiological phenotype differs mildly from that of DLL3 mutation-positive SCD and is variable, suggesting further heterogeneity [3].
• His two affected children were compound heterozygotes for this mutation and a novel missense mutation, G504D, the first putative missense mutation reported in the transmembrane domain of DLL3 [4].
• Direct DLL3 sequencing of individuals in two generations identified the affected father as homozygous for a novel frameshift mutation, 1440delG [4].
• 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 [5].

Biological context of DLL3

• The gene DLL3, mapped to 19q13 region, was recently found to be responsible for one form of AR SD; however, we did not find evidence of linkage between this 19q region and the SD segregating in our family, thus implying in genetic heterogeneity for AR SD [6].

Anatomical context of DLL3

• Using DNA from a chorionic villus sample, both linkage analysis of the DLL3/19q region and direct sequencing for the familial mutation demonstrated that the unborn fetus was an unaffected carrier [7].

Other interactions of DLL3

• 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 [8].

Analytical, diagnostic and therapeutic context of DLL3

• From our study cohort of cases of AVS, we have identified individuals and families with abnormal segmentation of the entire spine but no mutations in DLL3, and, in some of these, linkage to the DLL3 locus at 19q13.1 has been excluded [3].
• A consanguineous family of Turkish origin with ARSCD type 1 due to a homozygous DLL3 mutation requested genetic prenatal diagnosis [7].

References