If your hands and arms quiver when you write and do other tasks, you may have a common neurological condition called essential tremor (ET). As many as 7 percent of adults older than 65 suffer from ET, which may also affect the head and voice. In severe cases, it can be disabling. The cause of such shaking has long been mysterious. But researchers are beginning to uncover a biological explanation for the problem: they have found a gene that may contribute to its development as well as a pathological signature of the disorder in the brain.
Researchers knew that genetic factors underlie ET, as half or more of the cases run in families. But no one until now had succeeded in nabbing any of the responsible genes. To find such a gene, scientists at deCODE genetics in Iceland compared DNA blueprints from hundreds of tremor patients and thousands of unafflicted residents. In each person’s DNA, researchers looked at 305,624 single-nucleotide polymorphisms (SNPs), sites where the identity of the chemical unit (the pair of molecules that makes up each building block of a strand of DNA) commonly varies among people. Out of that analysis emerged one SNP that consistently differed between the patients and the others. The same chemical unit also turned out to be tied to ET in populations of patients whom the researchers recruited from Germany, Austria and the U.S.
The newly fingered SNP lies in a gene for a protein called LINGO1 that is present only in the brain and spinal cord—a distribution consistent with a role in neurological disorders, says neurologist Dietrich Haubenberger of the Medical University of Vienna in Austria, one of the study’s authors. The protein, which straddles the cell membrane, is thought to govern interactions among cells and to thereby influence neuronal integrity as well as function. LINGO1 also has been implicated in multiple sclerosis and Parkinson’s disease, but its precise role in these disorders and in ET is unclear.
Nevertheless, in the case of ET, some researchers theorize that variation in LINGO1 may preferentially affect cells in the brain’s cerebellum, a brain structure that edits rough motor programs to produce coordinated movements. Neurologist Elan Louis of Columbia University and his colleagues recently reported seeing degeneration within the brain’s cerebellum among individuals who had ET when they were alive. Such deterioration may reduce the quality of the motion editing in that brain structure, leading to tremors, Louis says.
Whatever LINGO1’s role in ET, the newly identified version of the gene does not by itself cause the disorder. Having one copy of the risky variant boosts a person’s chances of developing ET by 55 percent; having two copies confers a 140 percent greater risk—and the SNP contributes to the condition in only a fifth of cases. But although many more genes, along with external culprits, are likely to be involved, implicating the gene for LINGO1 in ET is an important step toward unraveling the roots of the condition.
Scientists hope that the emerging genetic and cellular story of ET ends with better treatments; today’s medications for the disorder are partially effective at best. “Studies like these that start to clarify the biology will form the basis of more biologically based therapies than we have today,” Louis predicts.
Note: This article was originally printed with the title, "Shaking Hands."
This article was originally published with the title Shaking Hands.
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7 Comments
Add CommentThe refresh rate of a display device is crucial in presenting a non-flickering image. I wonder if this gene is connected to the production of some substance that keeps the neurons in a steady-state (no pun intended). Perhaps there is an inability to resend the signal in a timely fashion. "Capacitors" not recharging quickly enough?
Reply | Report Abuse | Link to thisI have ET and am wondering which medications are most popular. I take primidone and sertraline for the anxiety that I believe has resulted from the ET. I especially would like to know if there is something to help my voice. The meds I take do help the tremors quite nicely. Thanks :)
Reply | Report Abuse | Link to thisThe website article the Nervous System - Part 2 - The Cerebellum, at www.cosmic-mindreach.com shows how the cerebellum meaningfully integrates sensory inputs from various sources with appropriate motor outputs, synapse by synapse. A precise insight into how this works may provide some help in resolving the problem.
Reply | Report Abuse | Link to thisAll about Tremor in GoPubMed.com http://www.gopubmed.com/search?q=Tremor[mesh]
Reply | Report Abuse | Link to thisTop authors, statistics, related diseases and biological processes.
My grandmother had ET and my mom has alzeheimer and her sister has ET...therefore I imagine that this current research is very useful to understand their health problems.
Reply | Report Abuse | Link to thisI, and many in my large family, have had ET since childhood. Many of us take meds to control the tremors. I take two keppras a day and two low dose diazepam. Does this kind of tremor differ from the ones that occur in old age only? Thanks for the info. I hope that a study would one day clarify this for us shakers.
Reply | Report Abuse | Link to thisThe 5HT1A receptor is involved in supplying neurons with the fuel they need to fire, as well as preventing them from breaking down. - Is 5HT1A somehow involved in ET? Are the neurons not firing often enough to keep the muscles in a steady-state and thus leading to tremoring?
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