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Table of Contents
chromosome - a grouping of DNA containing many genes; each cell in
the human body contains 23 pairs of chromosomes
DNA - deoxyribonucleic acid, structured molecule which carries
genetic information gene -
basic unit of heredity that determines the characteristics that are
inherited; composed of strands of DNA and usually contain the instructions
required to manufacture a protein
gene therapy - a treatment technique which attempts to modify a
person's genes
genetic counselor - see
article genetic testing -
examining a person's DNA for missing, extra, or altered genes which may
signal a disease human genome -
the complete set of human chromosomes, approximately 30,000 genes
MRI - Magnetic Resonance Imaging, non-invasive, diagnostic test which
uses a magnetic field to create internal images of a person
protein - an organic molecule which is a fundamental component of all
living cells and is essential to the proper functioning of a living organism
phenotype - the outward presentation of a condition
stem cell - early stage cell which has the ability to produce
specialized cells for use in various body parts, such as the heart or brain |
DNA, genetic testing, stem cells, gene therapy.
These words are everywhere in the media today. Genetics is a hot topic with a lot of promise and maybe a little
hype. Yet, for those affected by Chiari and syringomyelia, genetics
touches on some of the most personal issues there are: Will my
children get this condition? Did I already pass it on to them?
Is there any way to find out?
If anyone can help us understand the genetic aspects of these conditions, it
is Dr. Marcy Speer. Dr. Speer is an Associate Professor in the Section
of Medical Genetics at Duke University, a genetic epidemiologist, a board
certified Ph.D. medical geneticist, and a board certified genetic counselor.
In other words, she knows what she's talking about.
We put
Dr. Speer In the Spotlight to see if we could shed some light on the
subject: How and when did you first become
interested in genetics?
S: I became interested in genetics in high school when I learned
about Mendel's laws and about population genetics. Both the biological
and mathematical aspects of genetics were appealing to me.
How did you get interested in studying Chiari/SM?
S: I was approached by ASAP (American Syringomyelia Alliance
Project) several years ago. I'm not sure how they found me, maybe my
work on Spina Bifida. ASAP was interested in pursuing the genetic
contribution to the condition.
Could you describe your current work on Chiari/SM?
S: We're interested in two things. First, identifying if
there is a genetic contribution to Chiari, both with and without
syringomyelia. Once that is established, we want to identify the genes that
predispose people to these conditions in families.
Can you draw any early conclusions from your
work yet?
S: Yes, we've done a couple of things. One, we've
established that there is a genetic component in at least some cases.
In the first part of our research, we collected detailed information on
families - medical records, MRI's, etc.- and identified more than 100
families where two or more people are affected. This is consistent
with a genetic basis for the condition in some cases. Second, we
eliminated a few candidate genes and performed a genomic screen to identify
regions of interest.
If you discover a Chiari gene or genes, is
developing a test straightforward?
S: Yes, a test for whether someone carries the alteration is
straightforward. Interpreting what the genetic alteration means in a
given individual is difficult - when will they become symptomatic, how
badly, etc.?
Is it important to develop a test?
S: I don't have tunnel vision about the importance of genetics in
CM/SM. A lot of families have more pressing issues just in coping with
daily life. But, for life planning, having children, knowledge can be
important to some people, not all. Also, sometimes identifying the
genetic basis of a disorder can provide information about mechanisms and
this can give insight into better interventions.
Do you believe
that Chiari is a complex disorder (multiple genes, gene-environment
interaction)?
S: Complicated question, my guess is that the underlying genetics are
“simple” in nature, that within a family with a genetic predisposition, risk
is due to the involvement of a single gene. What will be complex about this
condition is that there is tremendous variability as to how it manifests
itself within families who would carry the same altered gene. When do
people become symptomatic? What defines what Chiari is? Who gets a syrinx
and is it just chance or under genetic influence? That’s probably where
either other genetic or environmental influences play into it – the
presentation of the condition.
If you discover
a Chiari gene or genes, how do you determine what percent of cases it
accounts for?
S: By studying large groups of individuals who are carefully phenotyped
and then looking at whether they have a particular genetic alteration or
not. That part can be straightforward.
Is it expensive
or cheap to determine the percent of genetic contribution?
S: Depends on the genetic change, some are easy and
straightforward, some are more subtle. So the approach is straightforward,
but the expense is variable.
Given the
relationship between Chiari Type 2 and Spina Bifida, do you think that Folic
Acid might play a role in Chiari malformations?
S: My gut feeling is ‘no’, but I can’t provide any solid support one way
or the other for that impression.
You are also a
genetic counselor; what is a genetic counselor?
S: A genetic counselor is typically a master’s level person who works
with a physician (medical geneticist) in dealing with patients and families
either diagnosed with or at-risk for a genetic condition. Genetic
counselors provide educational information - what’s the disease, what’s the
recurrence risk - as well as psychosocial assistance, dealing with the
stresses associated with the condition under question. I did primarily
genetic counseling in prenatal cases, for example advanced maternal age,
family history of birth defects, and for muscular dystrophies.
Currently, some
states screen all newborns for a number of genetic conditions. If a test
were developed for a “Chiari gene”, would you recommend that it be added to
the newborn screening?
S: The ideas about newborn screening are evolving so rapidly that I’m
not sure. Currently, most newborn screening involves situations where
either treatment/intervention is available following diagnosis; or
identifying cases early enough can provide important reproductive risk
counseling for at-risk couples. I’m not sure that Chiari would fit either
of these categories. On the other hand, genetics and genomics is advancing
so rapidly that our ideas of what information is “useful” is evolving.
Under what
circumstances would you recommend that the siblings, parents, or children of
a newly diagnosed patient have an MRI or a genetic test?
S: Right now, I think if there’s any question of symptoms of the
condition. One of the early issues that ASAP presented to me is that
sometimes symptomatic relatives were being denied diagnostic testing because
“it wasn’t genetic”, and hopefully some of our work has helped to prevent
that knee-jerk response.
There appears
to be an enormous gap between developing genetic screening tests and
developing effective gene therapies. Has anyone been successful in curing a
disease through gene therapy?
S: Yes, there have been some important successes ... There are lots of
trials on-going, and a few interventions, we now call it gene transfer, have
had really good success.
Is the genetic
research community getting frustrated at the complexity of using the
information that has been uncovered in the human genome?
S: Yes, everyone’s frustrated . . the science is moving
incredibly rapidly – really at lightning speed for research – but we have
limited successes in making it real from the interventional perspective.
Do you believe
there is, or has been, too much hype surrounding genetic testing and gene
therapies?
S: Depends on one’s perspective. I think that the
promise is there, and geneticists know that the real “pay-off” is about
10-15 years away. The risk is having the public think that the pay-offs are
sooner than we can really deliver, and then people getting frustrated.
From the patient’s perspective, really anyone who’s waiting for results,
the progress is interminably slow.
Do you ever get
concerned that the increasing pace of scientific discovery is not giving
society a chance to work through the ethical issues surrounding new
discoveries and technologies?
S: Yes, it’s a big issue. There’s a
difficult balancing act between bench science and practical applications.
What should be
done about this?
S: The government has done a lot, NIH (National Institute of Health)
has a whole group dedicated to these issues. In first world countries, like
the US, Canada, Britain, there are very sincere and dedicated efforts to
identify, understand, and think through the implications of the work we do.
How do you feel
about Pres. Bush’s stem cell decision?
S: Brilliant political move. He walked a very fine line. He kept
the door open without completely alienating his conservative base
Are stem cells
overhyped?
S: No, they offer great promise.
As a good
scientist you probably don’t like to speculate, but as an expert, please
speculate on the following:
Will you
develop a Chiari genetic screen?
S: I think that testing for Chiari from the genetic perspective
will definitely become available.
Is there any
chance for a gene therapy cure for Chiari? If so, how far in the future?
S: Not likely with today’s gene therapy techniques.
Many people are
diagnosed just as they are starting families. Should passing on this
disease be a consideration for patients thinking about having children? Or
for children who grow up with the disease as they become adults?
S: Wow, tough questions! One of the powers of this kind of work
is that it offers the option of additional information. One of the
things that I’ve learned from genetic counseling is that no one can predict,
not even the individual themselves, how they will utilize information. My
own perspective is that I think that the option for utilizing information
should be available and access should be by individual choice and not
dictated by society.
You’ve been
known to choke up when thinking about the children affected by the disease
you study – are they your motivation?
S: A big motivation. My motivation is I want to do things that
can be translated to real efforts and make a difference; that’s why I focus
on genetic abnormalities. The reproductive issues are near and dear to my
heart.
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In the Spotlight:
Marcy Speer, Ph.D.
Associate Professor
Section of Medical Genetics
Department of Medicine
Duke University
Qualifications:
Education:
Research Interests:
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Chiari 1/SM
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Spina Bifida
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Muscular Dystrophy
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Asthma
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Bipolar Disorder
Selected Publications:
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Speer
MC, Enterline DS, Mehltretter L, Hammock P, Joseph J, Dickerson M,
Ellenbogen R, Milhorat TH, Hauser MA, George TM. Chiari Type I
Malformation WIth or Without Syringomyelia: Prevalence and Genetics.
Journal of Genetic Counseling 12(4); August 2003.
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Speer
MC, George TM, Enterline DS, Franklin A, Wolpert CM, Milhorat TH. A Genetic
Hypothesis for Chiari Type 1 Malformation with or without Syringomyelia
(CM1/S). Neurosurgery Focus 8(3); March 2000.
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Milhorat TH, Chou MW, Trinidad EM, Kula RW, Mandell M, Wolpert C, Speer MC.
Chiari I Malformation redefined: Clinical, radiographical and genetic
features in 364 symptomatic patients. Neurosurgery 44:1005-1017, 1999.
Editor's Note:
Dr. Speer's work extends beyond the laboratory as she freely
donates her time and energy to help patient organizations.
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