In recent years researchers have identified several gene mutations that underlie familial hemiplegic migraine, a rare, inherited form of migraine. Although the genetic work is in early stages, it is already clear that these mutations disrupt the complex workings of the ion channels and pumps that regulate the activity of nerve cells. The genetic findings have helped convince many investigators that even common forms of migraine arise from abnormal activity by nerve cells rather than from blood-flow changes in the brain. This conclusion is reinforced by the discovery that three “migraine genes” also carry mutations that cause epilepsy, one of the first heritable diseases recognized to result from abnormal ion channel functioning. Such diseases are called channelopathies.
The genes implicated in the familial disorder include those listed below:
- CACNA1A encodes a major protein of a neuronal calcium channel called the P/Q channel.
- ATP1A2 carries the information for producing a protein that pumps sodium and potassium ions across the membranes of nerve cells to create the ion gradient used by ion channels.
- SCN1A is the most recently discovered familial hemiplegic migraine gene. It gives rise to a neuronal sodium channel.