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.
Patient 1 had profound motor and intellectual disability with moderate lissencephaly suggestive of RELN mutations and was shown to harbor a splicing homozygous RELN mutation.
Lissencephaly and subcortical band heterotopia are major malformations of cortical development due to abnormal neuronal migration and several genes have been identified including ARX, DCX, LIS1, RELN, TUBA1A, and VLDLR.
A number of neuropsychiatric disorders including autism, schizophrenia, bipolar disorder, major depression, Alzheimer's disease and lissencephaly share a common feature of abnormal Reelin expression in the brain.
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).