from Linkage Newsletter, Volume I, spring, 1995.
A Cajun cottage designed to replicate the farmhouses built by the
Acadians who came to Louisiana in the 1700's was the catalyst for genetic
research into Friedreich's Ataxia at LSU Medical Center. The cottage sits
among modern brick homes in the small town of Henderson, Louisiana,
population 2,000, located 12 miles east of Lafayette, in the heart of Cajun
country.
Ataxia is a family of diseases that destroys the brain cells governing
muscle control. There are both dominant and recessive forms. Friedreich's
Ataxia is a recessive form, meaning an affected individual has two copies of
the defective gene, one inherited from each parent. Dominant forms mean only
one copy of the defective gene is needed for an individual to be affected.
The story begins in 1982 when Dr. Mary Kay Pelias, a native of
Louisiana and professor in the Department of Biometry and Genetics, and Dr.
Robert Elston, a native of England and head of the Department, took a trip
through Cajun country as part of field work on another genetic research project.
Pelias had stopped her car near the distinctive cottage and was pointing out
architectural features when the owner, Evelyne Goller, came out and a
conversation ensued. Pelias talked about her fascination with Cajun
culture and Goller explained her work as a specialist in Acadian language
and culture at LSU in Baton Rouge. The two geneticists then explained their
work in linkage analysis, a method scientists use to find the location of a
disease gene on a chromosome. Each of us inherits 46 chromosomes (23 from
each parent), which contain about 100,000 genes. Linkage analysis cannot be
done without the participation of affected individuals and as many members
of their extended family as possible. It is the first step in identifying
the characteristics of the disease gene and ultimately effective treatments
such as gene therapy.
As a courtesy and without a second thought, they left business cards at
the end of the visit.
That chance visit became prophetic when Goller received an unexpected
letter from her cousin, Betty LeBlanc, who had lived all of her adult life
in Orange, Texas, located about 100 miles west of the Louisiana state line.
The cousins grew up together in the tiny town of Morse, Louisiana, which
"had a population of 500 when (she) left 32 years ago and still has a
population of 500," according to LeBlanc.
The town of Morse is 30 minutes from Lafayette and typical of the many
settlements established in the 1700s by French Canadians ousted by the
British from their farming villages in Canada. The odyssey of the
wandering Acadians is immortalized in the poem Evangeline written by Henry
Wadsworth Longfellow. Bonded by language, religion, culture and devotion to
family, the displaced Cajuns (Americanized pronunciation of Acadians) have
maintained an identify and a cohesion that is unique in the history of
America's melting pot.
LeBlanc's oldest child had been diagnosed by a neurologist in Houston as
having Friedreich's Ataxia. "He said the disease was so rare that we would
never find anyone else who had the disease." Not long afterwards, all six
LeBlanc children were examined during a free clinic in New Orleans sponsored
by the National Ataxia Foundation. Dr. Michael Wilensky, neurologist and
medical director, found that three of the six children had the disease.
There is no known cure for Friedreich's and the greatest hope to find one
lies in genetic research. The first symptoms are a stumbling walk, hand
incoordination and slurred speech that usually first appear at puberty. As
devoted parents, LeBlanc and her husband were more than frustrated in not
being able to do more to help their children. "We would have gone to see
anybody to help our children. We couldn't find anyone who was interested in
us. Doctors would say come back and see us in six months and charge $125,"
she explained.
Goller had heard about her cousin's children but did not connect their
condition to genetics until the visit by the LSUMC scientists. When Dr.
Bronya Keats, a medical geneticist originally from Australia, joined the
LSUMC faculty a few months later, Betty LeBlanc's story had a major impact
on the direction of her research.
Meanwhile, LeBlanc started her own research that would prove to be
invaluable. Using a combination of persistence and word of mouth, she found
five affected families in the town of Morse. "Five families in a town of
500 people! If the disease is so rare, why is it not rare in a town of 500?
I knew something important was going on," she said. She also did extensive
research into the genealogy of her family and that of her husband's, also
from Morse. Through information obtained by her mother, she quickly traced
their lineage back to the 1900 census tract. Ultimately, her research led
to two brothers who were probably two of the carriers of the gene when they
arrived in Louisiana with the other Frenchmen exiled from Canada.
Friedreich's Ataxia shows up in all races and ethnic backgrounds. One in
50,000 Americans has it, with one in 112 people cited as "carriers." The
frequency is higher In the Acadian population of southwest Louisiana. One
in 20,000 people is estimated as having the disease, with one in 70 people
cited as "carriers."
"Towns like Morse started with a handful of people and they branch out
and remarry," she explained. When LeBlanc presented her extensive family
history to Dr. Pelias and Dr. Keats, what geneticists call a "kindred," Dr.
Pelias exclaimed, "We've found a gold mine!"
"We were so thankful when we finally got to work with Dr. Pelias and Dr.
Keats because they were interested in us and just knowing that someone is
interested makes a big difference," LeBlanc said. "The greatest thing is
that they gave us hope, a chance for our children and their children.
Before there was nothing. No matter who we saw, they were not interested."
After several months studying the LeBlanc kindred, Dr. Keats told her, we
have enough genealogical information; now we need to do the blood work."
With a small grant from the National Ataxia Foundation, the field work began.
Blood is the most widely studied human tissue in genetic research because
samples are relatively easy to obtain and white blood cells are a plentiful
source of DNA, which is our genetic makeup. Convincing families in her
hometown to participate in the research was another matter, according to
LeBlanc. "Any disease can be destructive," she said. "If you are not
really strong in your relationships, Friedreich's or any disease can destroy
your family."
LeBlanc sometimes felt discouraged and credits Dr. Keats with keeping her
motivated. "She worked way beyond the doctor part. She works from a deep
commitment and a good heart," LeBlanc said.
She cites one proud family of high achievers who did not want to be
singled out. When one branch of the family had the disease, others took the
position that "this can't happen to me - that's my brother's family
problem."
"It's funny how the mind works," LeBlanc says, "fear of something is so
powerful." She tells of one elderly man who refused up to the time of his
death to give a blood sample. Later it was found out that he believed
Friedreich's Ataxia was caused by syphilis because his grandfather had had
syphilis. For many years the myth existed that syphilis caused ataxia
because the symptoms are similar to those of second and third stage
syphilis. "We need to change, show the truth," LeBlanc says. "This is not
caused by syphilis. We just happen to carry two defective genes and that is
where we have to put our energies and maybe in time doctors can change that
gene."
She tells the story of another affected family where the parents
divorced, with family members blaming each other. The husband had a sister
and brother with the disease so it was already known that Friedreich's was
part of his family. On the wife's side, there was no one with the disease.
Of the four sons who were born, three had Friedreich's Ataxia. "The wife
couldn't handle it and automatically blamed her husband," LeBlanc said.
"In order to cope, she had to say 'it's not my fault'. She never imagined
she was a carrier." When LeBlanc was able to show the husband how he and
his wife were related six generations back , he said "Wow! You can't
imagine how the weight lifted from my shoulders. All these years I have
been carrying the blame for this and now I see that my wife is also a carrier."
LeBlanc has witnessed how individuals change when they understand how they
are linked to families going back hundreds of years, that they are not the
only ones who are carriers of the gene. As a result, she is even more
committed to public education about the disease.
"We live in a time of blame. We think it's easier to blame than face the
problem. I never once felt blame. I don't want to place my energies on
blame. We've got to get rid of the old ways that keep people apart. The
more we educate, show, the more we understand."
With a recessive disorder like Friedreich's Ataxia, each child of two
parents carrying the gene has a 25 per cent chance of developing the
disease. There is a 50 per cent chance of being a carrier without showing
symptoms and a 25 per cent chance of being completely free. LeBlanc believes
that unless carrier parents openly talk about the disease and reach out,
there will never be help for affected children.
As a result of this pioneering work in genetics, the defective gene was
shown to be located on chromosome 9. This finding means that it is possible
to determine with high probability if unaffected close relatives of an
individual with Friedreich's Ataxia are carriers of the defective gene.
Research is continuing towards identifying the gene and the protein formed
from it.
"We need more research if we ever hope to find a cure," LeBlanc says.
"We're all in this. This will not end with my children. You're going to
see Friedreich's in future generations." The whole experience has deepened
her relationship to her native home. "People in Louisiana are good and
compassionate. You have to go away and come back to see what we have in
these beautiful Cajun families. I hope people can see in me the beauty of
the people I grew up with."
