Interview with Dr. Gail Herman
from November 1997
Gail Herman, M.D., Ph.D.
is a genetics researcher interested in Myotubular Myopathy. We asked her about some of the
Q. What updates can you give us
on the research that's going on in the U.S. and Europe? Also, now that the gene for the
X-linked version of MTM has been located, is there any effort to discover the role of this
gene in muscle development?
A. Several groups are performing
mutation studies to find the exact changes in the isolated MTM1 gene in boys with the
X-linked disorder. A paper from the laboratory of Dr. Herman and one from the laboratory
of Dr. Mandel in France with members of the European MTM Consortium were published in the
September issue of Human Molecular Genetics. Dr. Wallgren-Pettersson and other
members of the European Consortium are trying to collect information about patients and
correlate it with the mutations. While mutations were found in most patients, there are
clearly some families with the X-linked form (based on clinical severity, muscle biopsy,
and affected maternal male relatives) for which both groups have not as yet found
mutations. They could involve small changes which may be difficult to detect in this
change, or, perhaps, a small number of families have changes in another X-linked gene. It
is known that a very highly related gene lies very close to the MTM1 gene. We and others
may screen for changes in this related gene soon.
What the DNA studies mean is that
(1) when a mutation is found, we can establish for sure that this is MTM1 and we hope in
the future to predict better the clinical course; (2) for cases without a family history,
the carrier status of the mother should be able to be determined; (3) prenatal diagnosis
using DNA should be possible if the mutation is known.
There are also more basic
research studies going on in several laboratories to try to find out better what the MTM1
gene does. Some groups are trying to study the gene in the mouse and make a mutant form
in the mouse as a first step for
devising a therapy. The French group is trying to see where the gene works inside the
cell. We believe, based on the blood and liver and endocrine findings in some of the boys,
that the gene must act in other sites besides muscle. We are trying to study the
homologous gene in a much simpler organism - the fruit fly - to understand better how it
is involved in muscle differentiation and development. These studies will take longer but
are the best way to try to find out what the protein does which is necessary to see how it
can possibly be bypassed or corrected.
Q. Is there any progress or
research underway on the non X-linked versions of MTM?
A. For the non-X versions,
several groups, including ours, are collecting DNA samples from females with MTM and males
that are suspected to have a non-X form. In addition to the MTM1 gene and one related gene
near it on the X chromosome, there are at least 2 related genes that are not on the X
chromosome. Dr. Mandel's group in France is trying to isolate these non-X genes and then
look for changes in some of these patients. It is also possible that as the research finds
where MTM1 acts in the cell and in what pathway, other likely candidate genes for the
non-X cases will be identified and they can be studied.
Q. Now that you've moved to Ohio
State, what will be the focus of your work regarding MTM?
A. For my work, we will analyze
another set of patients for mutations in the next several months. I would like to get DNA
if possible in August and begin mutation analysis in September. We are not set up to
accept samples quite yet and it would be difficult to make cell lines. We could make DNA
if needed and freeze blood to make cell lines if necessary. We will also do some more
specialized studies to look at those patients where we have not yet found a mutation. I
also want to write up the clinical findings and need to get back to some of the families
and try to get a few more sophisticated tests done. Dr. deGouyon is still working on the
fruit fly gene at Baylor although this work is going pretty slowly right now. She has a
fruit fly gene and is trying to see what it does.
Q. There appears to be some
correlation between XMTM and several blood and liver disorders. What can you tell us about
A. I can't tell you much more
than you know about the blood and liver diseases. I think they are real risks and we don't
know yet who is at risk - my guess is that it is a subset of patients, perhaps based on
their exact mutation. I also don't know yet if you don't have symptoms by age 3 or 5 are
you in the clear? That is why we need more data. This would include getting better labs
and other information. I hope in the next year to write up a clinical grant to try to
study this in more detail.