The RELN gene provides instructions for making a protein called reelin. This protein is produced in the brain both before and after birth. Reelin is released by certain brain cells; then it attaches (binds) to specific receptor proteins. In the developing brain, this binding turns on (activates) a signaling pathway that triggers nerve cells (neurons) to migrate to their proper locations.
After birth, reelin likely plays a role in many brain processes, including the extension of axons and dendrites, which are specialized outgrowths from nerve cells that are essential for the transmission of nerve impulses. Reelin may also regulate synaptic plasticity, which is the ability of connections between neurons (synapses) to change and adapt over time in response to experience. Additionally, reelin controls the release of chemicals that relay signals in the nervous system (neurotransmitters).
At least six mutations in the RELN gene have been found to cause lissencephaly with cerebellar hypoplasia (LCH). This condition affects brain development, resulting in the brain having a smooth appearance (lissencephaly) instead of its normal folds and grooves. In addition, the brain region involved in coordinating movements is unusually small and underdeveloped (cerebellar hypoplasia). The RELN gene mutations that cause LCH lead to a complete lack of reelin. As a result, the signaling pathway that triggers neuronal migration is not activated. Without reelin, neurons are disorganized, the normal folds and grooves of the brain do not form, and brain structures do not develop properly. This impairment of brain development leads to intellectual disability, delayed overall development, movement problems, and other signs and symptoms of LCH.
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Studies have shown certain variations (polymorphisms) in the RELN gene to be associated with an increased risk of psychiatric disorders such as schizophrenia and bipolar disease. Women with these polymorphisms are at particular risk of developing bipolar disease. In addition, certain genetic changes that result in a decrease in production of reelin (but not a complete absence) may be a risk factor for autism spectrum disorder, which affects communication and social interaction. However, other studies have not supported these findings. Many genetic and environmental factors are believed to contribute to these complex conditions.