PAFAH1B1 gene
The PAFAH1B1 gene is essential for proper neuronal migration and brain development, with mutations linked to severe neurological conditions.
Normal Function
The PAFAH1B1 gene (also known as LIS1) provides instructions for a protein that is a subunit of the platelet-activating factor acetylhydrolase 1B (PAFAH1B) complex. This complex regulates the levels of platelet activating factor (PAF) in the brain, which is involved in neuronal migration—the movement of nerve cells to their proper locations during brain development.
The PAFAH1B1 protein also plays a structural role by interacting with the cell's cytoskeleton, specifically microtubules. These interactions are critical for cell division and the movement of neurons.
Health Conditions Related to Genetic Changes
Isolated lissencephaly sequence
Variants in the PAFAH1B1 gene can cause isolated lissencephaly sequence (ILS), where the brain develops a smooth surface instead of its normal folds and grooves. This leads to severe intellectual disabilities and recurrent seizures (epilepsy) beginning in early childhood. These variants reduce the amount of functional protein, impairing the ability of neurons to migrate correctly.
Subcortical band heterotopia
This condition is often considered part of the same disease spectrum as ILS. It results from PAFAH1B1 variants that alter the protein's structure or length, affecting its ability to interact with microtubules. Symptoms include developmental delays, intellectual disabilities, and drug-resistant seizures, though they are typically less severe than those seen in ILS.
Miller-Dieker syndrome
This syndrome is caused by a deletion of genetic material on chromosome 17 that includes the PAFAH1B1 gene. Individuals with this condition have only one copy of the gene instead of two, resulting in a shortage of the PAFAH1B1 protein. This deficiency leads to lissencephaly, intellectual disabilities, seizures, and distinctive facial features.
Other Names for This Gene
- LIS1
- LIS2
- MDCR
- NudF
- PAFAH
- platelet-activating factor acetylhydrolase, isoform 1b, alpha subunit
