Scientists have identified a genetic mutation that causes common migraines, possibly the first ever to be described. The findings, published in Science Translational Medicine, puts us one step closer to understanding the pain pathways that cause migraines.

"And, as we come to a clearer understanding, we can start thinking about better therapies," said senior investigator Louis J. Ptáček, an investigator at HHMI and a professor of neurology at University of California, San Francisco. "There are good drugs now, but they only help some patients, some of the time. The need for better treatments is huge."

The earliest descriptions of migraines date back at least 2,000 years; yet, despite its long connection to human existence, very little is known about what causes the disease.

The primary symptoms of common migraines are one-sided headaches and nausea; however, nearly one-third of sufferers experience "auras" — distortions in their sensory perception — before each episode begins

Researchers were able to identify a specific genetic mutation connected to migraines by looking at how migraines affected different members of the same family.

The family in question initially went to UCSF to seek treatment for severe migraines — one person had an episode every other day for a decade — but a follow-up psyche evaluation revealed that several members had a rare sleep disorder: familial advanced sleep phase syndrome (FASPS). Sometimes called "morning lark" syndrome, people with FASPS go to sleep unusually early in the evening and wake early in the morning.

The researchers discovered a mutation in a gene that controls sleep-wake cycles: the casein kinase 1 gene. After screening a database of blood samples from FASPS patients, a second family that suffers from severe migraines was discovered with a similar mutation in this sleep-regulating gene.

In other words, the genetic mutation that causes FASPS may also cause migraines.

To follow up on these observations, Ptáček and team went to the lab and worked with genetically-modified mice. The results were a success: mice with the same genetic mutation displayed some features of migraines.

"Obviously, we can't measure headache in a mouse," Ptáček noted, "but there are other things that go along with migraine that we can measure."

For example, the mice had changes in their brain activity that mimic what is seen with migraine auras and exhibited a heightened sensitivity to pain.

Mutations have been previously implicated in rare forms of migraines associated with muscle weakness, but a solid genetic basis for common migraines with auras has never described until now

"This is the first gene in which mutations have been shown to cause a very typical form of migraine," said Ptáček. "It's our initial glimpse into a black box that we don't yet understand.