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Dr.
Alan Beggs laboratory
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Beggs Laboratory |
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Dr. Alan Beggs (front, 3rd from left)
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The diagnosis of nemaline myopathy (NM) includes patients who have muscular
weakness and other special medical needs. The most common medical problems include
weakness of the respiratory muscles and those in the face, arms, legs and the
trunk as well as low muscle tone. Those interested in obtaining clinical information
about nemaline myopathy, should contact Dr. Susan Iannaccone, a paediatric neurologist
who has been involved in the care of many patients with nemaline myopathy.
Genetics. Currently, we know of at least five different genes that are
associated with NM. These genes are known by their abbreviations: ACTA1, NEB,
TPM2, TPM3, and TNNT1. Each one of these genes carries instructions to make
a protein that is important for muscle function. The proteins these genes make
are called: actin, nebulin, tropomyosin 2, tropomyosin
3, and troponin T, respectively. A person with NM may have an alteration
in any one of these five genes, resulting in a protein that does not work properly.
Since there are patients who have nemaline myopathy but no detectable gene alteration,
we suspect that there may be other genes that are involved in the cause of this
condition. This is why our group is also looking for alterations in other genes
as well. Since NM is a condition that arises from gene alterations, it may be
passed on from parents to children. There are some families, however, in which
NM arises for the first time, with no previous family history of the disorder.
We say that in these families NM occurred sporadically. Some families have contacted
us to express interest in learning the recurrence chance of NM and how it is
passed on in their family. Often, the only way to know this information is through
genetic studies.
Genetic testing for NM. It is important to know that currently, there
is no routine clinical genetic testing available for nemaline myopathy. However,
patients in the Americas and the Caribbean can participate in the research studies
done at our laboratory, located at Boston Children's Hospital. For patients
located in other parts of the world, laboratories in Helsinki and Western Australia
are doing similar studies as all three groups collaborate through the International
Consortium on nemaline myopathy, sponsored by the European Neuromuscular Center.
In our laboratory in Boston, we focus on understanding the various genes and
proteins involved in NM as well as in other neuromuscular diseases.
Research at the Beggs Lab. To achieve our goal, we aim to enrol volunteer
patients with nemaline myopathy and their families. For our studies, a sample
of blood from the patient as well as all consenting first-degree relatives (mother,
father, siblings, and any children) is required. We will extract DNA from the
blood sample and screen candidate genes that may be involved in the cause of
nemaline myopathy.
In addition to the DNA studies, we need a muscle sample that is often left over
after a patient's diagnostic test. Muscle samples are extremely important for
confirming the results of DNA testing as well as for studies that would allow
us to determine which genes are active in the muscle of patients with nemaline
myopathy and which are not. These experiments, known as microarray-based
gene expression studies, are a new technology that provides information
about thousands of genes at once. With the information derived from these microarray
studies, we may be able to discover new treatments for NM as well as develop
better tests. Therefore, if you are the parent of a child with NM, or if you
yourself are affected, you may be able to help us reach these goals by participating
in our research, if you wish. There is no cost for participating in this study.
Any incidental charges, such as shipping or cost of the blood drawing, if not
automatically covered by the family's health insurance, may be billed to our
lab. Travel to Boston is not required and individuals from any part of the world
can participate. For more information, please contact Elizabeth Taylor,
genetic counselor at Dr. Alan Beggs' laboratory.
Recent research findings. According to Dr. Beggs, approximately 15 out
of 100 (15%) patients with nemaline myopathy have alterations in the gene coding
for the protein called actin. It is also thought that potentially up to half
the patients with nemaline myopathy have alterations in the gene coding for
nebulin, a large protein found in the muscle. Development of better tests for
these nebulin changes is a primary goal in the research as there are currently
no effective methods for this due to the large size of the nebulin gene. Alterations
of the tropomyosin 2, 3 or troponin genes are much more rare, probably accounting
for less than 5-10 out of 100 (5-10%) of cases in total.
Reporting patient results. Because our laboratory is a research laboratory,
we cannot release individual results directly to patients. This is because in
the United States, the Clinical Laboratory Improvement Act/Amendment (CLIA)
only provides authorization to clinical laboratories to do so. However, if we
do obtain information that might be significant to the family, we can have these
results confirmed and reported by a CLIA-certified clinical laboratory if the
family desires it. Although participation in research is free of cost, there
is usually a charge associated with confirming results through the clinical
lab. The clinical laboratory fees, nevertheless, are usually covered by most
health insurance policies. It is also important to know that our work consists
of research studies of indefinite duration. Therefore, due to the unpredictable
nature of these studies, it is unlikely that we would make any clinically-relevant
findings in the near future. However, participants and/or their physicians are
welcome to contact us anytime for an update on the research. Regardless, the
participation of patients and their families is a tremendous and generous contribution
toward our understanding of nemaline myopathy, which is certain to help towards
the development of more effective diagnostic tests and treatments to benefit
patients and their families in the future.
Elizabeth Taylor DeChene, M.S., C.G.C.
Research Genetic Counselor
Children's Hospital Division of Genetics, Enders 5
300 Longwood Avenue
Boston
MA 02115, USA
Phone: (617) 355-2185
Fax: (617) 355-7588
Genetic Research on Nemaline Myopathy:
Information for Patients and Families Boston Children's Hospital
We are a group of scientists and doctors studying the genes that may be involved
in the cause of muscular disorders. One of our goals is to determine which
genes and proteins are involved in nemaline myopathy, a rare muscular disorder.
With the generous help of enough candidate families, we may be able to learn
information that will hopefully help us understand this disorder, improve diagnosis
and develop new treatments. We currently know of five different genes associated
with nemaline myopathy. Each of these genes carries instructions to make a protein
that is important for muscle function. These proteins are called actin,
nebulin, tropomyosin 2, tropomyosin 3, and troponin
T. An alteration in any of these genes can result in a non-working protein,
causing nemaline myopathy. Some patients do not have an alteration in any of
the genes we know about. For this reason, we suspect that there may be additional
genes involved in nemaline myopathy yet to be discovered. If you are the parent
of a child with nemaline myopathy, or if you yourself are affected, you may
be able to make a meaningful difference by helping us find new genes and proteins
associated with nemaline myopathy.
Participation consists of:
1) Informed Consent If you are interested in learning more about us, we will
send you a consent form that explains the research study in more detail. Each
family member who decides to participate will need to sign a different consent
form. If the participant is a minor, a parent/guardian will be the one who provides
consent.
2) Medical information and family history Once you have decided to participate
in our study, we will ask your permission to obtain relevant medical records,
such as a muscle biopsy report, from your physician. We may also ask you some
questions about your family medical history. This can be done through a brief
telephone interview.
3) Blood sample We ask for a small blood sample from all available and consenting
family members. This blood sample will be used to isolate the genetic material
(DNA). The DNA will be screened for alterations in genes that may be involved
in nemaline myopathy. We can arrange the blood draw either through a participant's
physician or a nearby medical facility. All costs for the blood draw are paid
by our laboratory.
4) Muscle tissue from an existing biopsy Studying muscle from a person who
has nemaline myopathy can tell us a lot about the genes and proteins involved
in the disease. We can help find out if any frozen tissue is still available
from an existing muscle biopsy and, with your permission, arrange to have it
shipped to our laboratory. Alternatively, if you or your child is scheduled
to undergo a surgical procedure in the near future, this may provide an opportunity
to donate a muscle specimen. With some procedures, it is possible for the surgeon
to remove a small piece of muscle without any additional risk or discomfort
to the patient. Cost and time commitment: Participation in this study is free
of charge. Travel to Boston is not required and individuals from anywhere in
the world may participate. The phone interview, blood draw, and paperwork should
take no more than 2 hours to complete.
Reporting of Results:
It is possible that we identify a gene alteration as the cause of the muscle
disease in your family. In this case, and with your permission, we will be
happy to make it available to you. As a research laboratory, we are not authorized
to release patient results, but we can refer you to a laboratory that would
confirm our findings and report the results to your healthcare provider.
If you would like to know more about this study, please contact:
Children's Hospital Division of Genetics
Enders 5
300 Longwood Avenue
Boston
MA 02115, USA
Phone: (617) 355-2185
Fax: (617) 355-7588