Besides LIS2 and ADLTE, <i>RELN</i> and/or other genes coding for the proteins of the Reln intracellular cascade have been associated substantially to other conditions such as spinocerebellar ataxia type 7 and 37, <i>VLDLR</i>-associated cerebellar hypoplasia, <i>PAFAH1B1</i>-associated lissencephaly, autism, and schizophrenia.
We found molecular and genetic evidence that reductions in Reln expression contribute to GCp proliferative defects and cerebellar hypoplasia in GCp-specific Chd7 mouse mutants.
The girl's brain magnetic resonance imaging (MRI) findings, including pachygyria and severe cerebellar hypoplasia, were identical to those seen with RELN point mutations.
Identifying these mechanisms has shed light on typical human neuronal migration disorders such as periventricular heterotopias (disorder of migration initiation linked to filamin), type I lissencephaly (cytoskeletal abnormality linked to Lis1, a microtubule-associated protein), double cortex syndrome (cytoskeletal abnormality linked to doublecortin, a microtubule-associated protein), or lissencephaly plus cerebellar hypoplasia (reelin defect).