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Genetic
testing can identify gene mutations that put adults
at greater risk for developing serious disorders and
diseases, such as DVT’s, high cholesterol and unexplained
miscarriages. As a result, simple preventive measures
can save lives and reduce disability.
Imagine the person sitting
across from a genetic counselor. Typically, it’s
a parent seeking microscopic answers to questions raised
by a child’s physical symptoms, or a couple who’s
undergoing prenatal screening. But increasingly, it’s
an adult with a family history of cancer, heart disease,
or another heritable (inherited) medical condition.
“Adults whose parents
or siblings have a heritable disease often want to know
if they’ll get it, also,” says Marvin
Schwalb, PhD, director of University Hospital’s
Center for Human and Molecular Genetics and professor
of microbiology and molecular genetics at New Jersey
Medical School. “Genetic testing usually doesn’t
answer that question directly, but it can answer whether
a person is at an increased risk—or is predisposed—
to have it.”
By nature, everyone is
born with an inheritance: 23 chromosomes from each parent
that arrange themselves into 23 pairs in each cell.
Chromosomes are made up of genes, the body’s blueprint.
A gene can change (mutate), and the altered gene can
be passed on within a family. These altered genes, alone
or in a pair (one from each parent) cause the body to
function differently, often in an imperceptible way,
but sometimes with serious results. Also, many genes
have common variations called polymorphisms, which can
increase the risk of certain diseases.
When the inheritance
pattern is dominant, only one flawed gene in a pair
is necessary for a condition to occur. A person who
has an autosomal dominant disorder like neurofibromatosis
1, which causes tumors to grow along the nerves, may
have a parent with the condition. The chances are 50-50
that a parent will pass along an autosomal dominant
disorder to a child.
| Autosomal
Dominant Disorder |
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An autosomal recessive
pattern is different: both parents “carry”
one altered gene. There’s a 50 percent chance
that a child will also be a carrier; a 25 percent chance
that a child will have received one altered gene from
the mother and one altered gene from the father, and
thus have the disorder; and a 25 percent chance that
a child will neither be a carrier nor have the disorder.
Sickle cell anemia, a blood disorder, is an example
of an autosomal recessive condition. The mother and
father of a child with sickle cell anemia themselves
each have one altered sickle cell gene, but because
they each also have an unaffected gene, they do not
have the condition.
| Autosomal
Recessive Disorder |
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In
diseases associated with altered recessive genes,
both parents -- although disease free themselves
-- carry one normal gene and one altered gene.
Each child has one chance in four of inheriting
two altered genes and developing the disorder,
one chance in four of inheriting two normal
genes, and two chances in four of being a carrier
like both of the parents. Image and caption
provided by Science
+ Literacy for Health, a project of the
AAAS Directorate
for Education and Human Resources.
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In conditions such as
color blindness or hemophilia, the gene is on the X
chromosome; a son who receives the defective copy from
his mother will have the disease.
| X-Linked
Recessive |
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In
this example, an unaffected woman carries one
copy of a gene mutation for an X-linked recessive
disorder. She has an affected son, an unaffected
daughter who carries one copy of the mutation,
and two unaffected children who do not have
the mutation. Image and caption provided by
the U.S. National
Library of Medicine.
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Like interpreters of
a complex code, scientists have discovered the genetic
makeup of many conditions frequently diagnosed early
in a person’s life, such as cystic fibrosis and
muscular dystrophies. They’ve also made inroads
in determining the genetic underpinnings of diseases
or disorders typically found in adults. For these conditions,
a blood test or a sample of cheek cells can provide
valuable information about a person’s likelihood
of acquiring a hereditary condition.
Focusing
On Adults
Genetic testing is nothing
new at University Hospital. For 14 years, the Center
for Human and Molecular Genetics has tested and counseled
many people seeking genetic information—about
1,000 patients a year. Most of the testing has focused
on detection of birth defects. Now, with the new discoveries
of the Human Genome Project, it is possible to determine
the genetic risks for many diseases in adults, and to
make this information available, the Center has a new
initiative: the Adult Onset Genetic Disease Program
at University Hospital.
The adult onset program,
explains Dr. Schwalb, is an interdisciplinary endeavor
designed to help identify, diagnose, and treat adult
onset inherited conditions. “For now, we are focusing
on thrombotic conditions, which are characterized by
abnormal blood clotting; several predisposing forms
of coronary diseases, such as familial hypercholesterolemia,
in which high LDL cholesterol levels and even heart
attacks can occur at early ages within a family; and
breast cancer and colon cancer,” he says. “These
conditions were chosen because if a genetic mutation
is identified, physicians can offer simple, yet potentially
life-saving interventions for the patients and other
family members. There’s no reason to test for
something that we can’t do anything about.”
Over time, as additional tests are developed, he says,
the adult program will expand.
People can either be
referred for testing by their physician or call the
Center directly (see the phone number at the end of
the article). The Center is staffed by five genetic
counselors. After taking a detailed family history,
the counselor will arrange for the appropriate test.
If test results come back negative, the patient will
receive a letter stating as such. When the results are
positive for a mutation, the person will be called and
asked to return for a follow-up appointment with a genetic
counselor. “It’s important that he or she
receives the information and has a counselor present
who can interpret the results, answer questions, and
explain what interventions are available,” says
Dr. Schwalb. “The patient can go back to his or
her physician for treatment or be referred to a University
Hospital physician.”
The Adult Onset Genetic
Disease Program’s counselors are highly trained
and can answer many questions about a genetic disorder
and the possible treatment options. However, their response
to the most frequent question they are asked may be
disappointing. That question is, “If this were
you, what would you do?” Says Dr. Schwalb, “We
aren’t you, and would never presume to be. However,
the counselors do provide a vast amount of information
the patient can use to make a decision.”
Early
Warning
In some cases, genetic
testing can shed light on otherwise unexplainable physical
events. Take a family where there’s a history
of seemingly healthy people dying unexpectedly. From
a blood test, geneticists can tell whether there are
defects on genes that maintain electrical balance in
the heart. These gene mutations are associated with
Long QT Syndrome, where cardiac electrical abnormalities
can trigger arrhythmia, an irregular, very fast heart
rhythm. The irregular rhythm can lead to loss of consciousness,
cardiac arrest, or death. There are, of course, non-genetic
causes of Long QT Syndrome, including certain medications
and mineral imbalances. However, if the Long QT mutations
are detected, medications known as beta blockers, which
can slow the heart rate, may be an appropriate first
course of treatment. Long QT patients who’ve had
cardiac events and do not respond well to beta blockers
alone could be candidates for pacemakers or implantable
cardioverter-defibrillators.
Similarly, two or more
unexplained miscarriages could also warrant genetic
testing. Here, geneticists are looking for one of several
gene mutations associated with abnormal blood clotting.
The prothrombin II mutation can cause an increase in
coagulation, or blood clotting. In pregnancy, clotting
in the placenta can reduce blood flow to the fetus,
which can contribute to growth retardation, stillbirth,
or miscarriage. A study published in the Archives of
Internal Medicine this year reported that women with
prothrombin II or Factor V Leiden mutations were at
twice the risk of having two or more miscarriages. A
pregnant woman with these mutations would be closely
monitored by her obstetrician and, in some cases, be
prescribed heparin (or advised to take a daily baby
aspirin) to prevent blood clotting.
One of the more common
thrombotic conditions is Deep Vein Thrombosis (DVT),
also known to airline travelers as Economy Class Syndrome.
DVT is another excellent example of a medical condition
where non-genetic and/or genetic factors can come into
play. When a person is immobile for long periods of
time (such as when seated for hours on long flights
or lying in a hospital bed following an operation),
blood can pool in the veins and clot. If the blood clot
breaks off and travels to the lung, it could cause a
serious problem—pulmonary embolism, a leading
cause of death in the United States.
Some people develop DVT
for seemingly no reason at all. In these patients, DVT
often has a genetic link. In 1994, scientists identified
Factor V Leiden, the most common DVT mutation. It occurs
in between 3 percent and 8 percent of the general population.
Other genetic mutations—prothrombin II and Protein
S and Protein C deficiencies—can cause a life-threatening
increase in blood clotting, as well. A person who has
had DVT and, after testing, shows any of the genetic
predispositions for the condition, will typically be
prescribed a medication such as Coumadin® (warfarin),
which reduces the blood’s ability to clot.
Dr. Schwalb believes
that not only should a person who’s had an unexplainable
DVT incident undergo genetic testing; if their bloodwork
indicates a mutation such as Factor V or prothrombin,
all immediate relatives should be made aware. That holds
true for any heritable medical condition. “Genetic
testing is a family matter,” says Dr. Schwalb.
“Whether or not a person chooses to be screened
is up to the individual, but with genetics, family is
always part of the equation.”
Colorectal cancer, another
of the conditions the University Hospital program tests
for, is highly treatable in its early stages. While
most colorectal cancers are sporadic and caused by a
variety of factors, including diet, sedentary lifestyle,
and age. About 5 percent of colorectal cancer patients
have an inherited form of the disease. With hereditary
nonpolyposis colorectal cancer (HNPCC), there is mutation
on any of several mismatch repair genes, whose job it
is to prevent DNA errors during replication. People
who’ve inherited an altered mismatch repair gene
have about a 70 percent to 80 percent lifetime chance
of developing colon cancer. A rare but aggressive type
of hereditary colon cancer, familial adenomatous polyposis,
or FAP, involves a mutation of the adenomatous polyposis
coli (APC) gene. FAP causes hundreds of polyps to grow,
often when patients are in their teens. The polyps become
cancerous, and ultimately, removing the colon may be
the only cure.
Colorectal cancer is
usually symptomless early on, so testing a person with
a family history of the disease could well be a life
saver. “In the general population, screening for
colon cancer begins at age 50. An intervention for people
with a genetic predisposition could be screening at
a much earlier age and removal of polyps,” says
Dr. Schwalb. “Some teenagers with the APC gene
mutation have chosen to have their colon removed. This
might sound extreme, but often, they’ve watched
other family members suffer with colon cancer or die
at a young age. After the colectomy, they go on to live
otherwise normal lives.”
Elements
of a Quality Program
Genetic testing has piqued
the public interest, to the point that on-line testing
firms have grown more common. Convenient and accurate,
possibly, but Dr. Schwalb says these “boutiques”
don’t offer some crucial elements of a genetic
testing program. “The science may be legitimate,
but the follow-up care isn’t necessarily there,”
he says. “It’s done without the personal
support of specially trained genetic counselors who
explain test results to the patient and the rest of
the family.”
In most cases, genetic
testing is covered by insurance. That’s good,
because the tests can be quite expensive. Some people
worry that an insurance company may deny coverage based
on test results, but Dr. Schwalb says that it hasn’t
been an issue. “An insurance company isn’t
going to deny coverage on the basis of a predisposition—something
that might or might not happen,” he says. Another
concern—patients’ privacy—is taken
very seriously by genetic testing centers for ethical
and legal reasons. The New Jersey Genetic Privacy Act
regulates the release of genetic test results and bars
insurers and employers from discriminatory practices
based on genetic information. The Adult Onset Genetic
Disease Program releases test results only to the patient
and the referring physician.
In a few cases, receiving
the results of a genetic screening can be emotionally
devastating, and for those people, the Center will recommend
counseling support. But for the majority, the implications
are more positive. “Most of our patients feel
empowered by having the information. Often, they know
that a certain disease runs in their family; now they
can make decisions about intervention treatment, if
warranted,” says Dr. Schwalb. “And remember
that a lot of people get good news.”
For more
information or to make an appointment, call the Adult
Onset Genetic Disease Program at University Hospital
at (973) 972-7859.
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