DSCAM - Clinical Significance

Clinical Significance

The role of Ig-CAMs in human development and disease is only beginning to be elucidated. This may be of particular interest with respect to the DSCAMs, as DSCAM maps to chromosome 21 in a region critical for the neurocognitive and other defects of Down Syndrom and DSCAML1 maps to chromosome 11 in a region whose deletion is associated with 11q deletion syndrome. This gives rise to neurocognitive defects and a subset of other defects which are similar to those seen in DS, including psychomoter retardation, strabismus, epicanthus, telecanthus, carp-shaped upper lip, low-set dysmorphic ears, and cardiac defects. The level of DSCAM expression is increased by more than 20% in the DS brain. Given its identity as a potential neural morphogen and its expression in the cerebral and cerebellar cortices from the earliest stages in their development, it is not unreasonable to suggest that this level of DSCAM overexpression may contribute to the pre- and post-natal defects of DS, particularly, the cerebral and cerebellar hypoplasia and the abnormalities of the dendritic tree. Further, a role for DSCAM overexpression in contributing to the defects of cortical lamination seen in DS is supported by the fact that disruptions in other genes expressed by Cajal–Retzius cells, such as Reelin andLIS1, cause severe defects in neuroblast migration and cortical lamination.