Children with Miller-Dieker syndrome (MDS) have lissencephaly (smooth brain surface) and facial dysmorphisms, while patients with simple lissencephaly have no dysmorphic features. All persons with MDS have hemizygous microscopic or submicroscopic deletions of 17q13.3 while some, but not all, patients with simple lissencephaly have microdeletions of 17q13.3. These findings suggest that MDS is a contiguous gene syndrome, in which the deletion of several unrelated genes, including a gene for lissencephaly, produce a complex recognizable phenotype. We have isolated three genes in the mouse that correspond to genes mapped to the MDS region of 17q13.3. We have shown that the gene order and distance between genes is conserved between mouse and humans by FISH analysis. We are creating targeting constructs that will inactivate each of these genes, as well as introducing aloxP site into each gene to allow creation of microdeletions through site specific recombination.
