Scientists Discover Key Gene Mutation Behind Lou Gehrig's
WEDNESDAY, Sept. 21 (HealthDay News) -- Researchers have
identified a genetic mutation common to roughly one-third of two
devastating neurological disorders, amyotrophic lateral sclerosis
(ALS) and frontotemporal dementia (FTD).
ALS, also known as Lou Gehrig's disease, destroys the motor
neurons of the brain and the spinal cord, which are responsible for
voluntary movement. ALS patients become progressively more
paralyzed, and often die within a few years of diagnosis.
FTD is a type of dementia that occurs when the frontal and
temporal anterior lobes of the brain atrophy. People with FTD
develop erratic behavior, emotional problems, trouble communicating
and difficulty with walking and other basic movements.
As with ALS, FTD is often fatal within a few years, according to
the U.S. National Institute of Neurological Disorders and Stroke
Now, an international team of researchers has found that about
one-third of people who have familial ALS and FTD have a mutation
on a specific gene, C9ORF72, that resides on chromosome 9.
The finding has led researchers to suggest that rather than
being two separate diseases, ALS and FTD should be thought of as
one condition with symptoms that lie along a spectrum.
"When we look at the families in our study, many of the patients had ALS, many had FTD and the remaining had ALS and FTD," said senior study author Dr. Bryan Traynor, chief of the Neuromuscular Diseases Research Group at the U.S. National Institutes of Health. "Although clinically they have always been described as two separate diseases, they are overlapping. We now believe that ALS and FTD are actually different clinical manifestations of the same disease."
The hope, he added, is that a better understanding of the
underlying genetic root cause of both diseases could lead to more
"It gives us a target. It's a shortcut," Traynor said. "We now have a map. Instead of having to figure out what's at the end of every street, we now know the routes to the city and we can get there a little bit quicker."
In the same issue of the journal, a team led by Mayo Clinic
researchers in Florida independently identified the same mutation
in families affected by both ALS and FTD.
The two studies are published in the Sept. 21 online issue of
As many as 20,000 to 30,000 people in the United States have
ALS, and some 5,000 people in the United States are diagnosed with
the disease each year, according to NINDS.
People with ALS often first notice they're having difficulty
moving a hand or swallowing, explained Lucie Bruijn, chief
scientist with the ALS Association. Then, over the course of a few
years, they rapidly lose strength, the ability to move their arms,
legs and body, and finally, the ability to breathe without
In about 90 percent to 95 percent of ALS cases, there are no
known risk factors or triggers for ALS. But, between 5 percent and
10 percent of cases run in families, according to NINDS.
FTD also often runs in families, with about 20 percent to 40
percent of cases of FTD inherited, experts said.
While the conditions can have different symptoms, physicians
have long known that some people with ALS also develop symptoms of
FTD, while FTD can also share some characteristics of ALS, Bruijn
Those observations led researchers to hunt for a genetic
mutation that might be present in both conditions. That search was
eventually narrowed to an area of chromosome 9, but for years
geneticists were stymied in honing in further, Traynor said.
In the current research, Traynor and his colleagues from Canada
and Europe analyzed the genetic sequences of 402 Finnish patients
with familial ALS, 75 Finnish patients with FTD, 268 patients of
European descent with ALS, as well as several hundred healthy
Finland has the highest rates of ALS in the world, Traynor
The investigators found about 50 percent of the Finnish ALS
families had the mutation, along with about 38 percent of the
families of European descent (or about 8 percent of the total
population of people with ALS) and 29 percent of those with
The mutation causes a repetition of a DNA sequence over and over
Though the repeat expansion clearly causes problems, much
remains unknown. Researchers don't know what makes one person
develop ALS and another develop FTD.
Nor do they know what the C9ORF72 gene does in the body. The
mutation is on a non-coding section of the gene, meaning that it
doesn't produce a protein, Bruijn said. Researchers believe the
gene mutation might interfere with RNA transcription, a basic
process of a cell, leading to a toxic build-up of RNA, she
"They have found the gene error, but they don't yet understand the biology," she said.
Researchers also found the mutation is present in some people
with sporadic ALS, meaning that it doesn't run in the family,
although this wasn't the focus of the study.
Bruijn called the findings a reason for hope, enabling groups
studying ALS and FTD to join forces in finding a treatment.
"It's a very exciting handle on what is going on in ALS, FTD and both, and how this mutation is causing the disease in both cases," she said. "It's the beginning of new areas of discovery that ultimately will pave the way for new treatments."
The U.S. National Institute of Neurological Disorders and Stroke
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