Familial Motor Neurone Disease - Imperial College London

Familial Motor Neurone Disease

The Disease

Familial MND (FMND) is very rare. It accounts for only about 5%
of the cases of MND. The great majority of cases of MND (95%)
are sporadic where only a single isolated case occurs in a family.
FMND affects more members of the same family than be
accounted by chance. There is evidence that the disease is present
in one of the parents of the affected person and has been passed
on to some (not all) members of following generations.

The Importance of Research

It is important that researchers can examine the familial form of
the disease because it provides us with a focus for looking at the
cause of MND. The familial and sporadic forms are clinically
indistinguishable, so it is likely that a common abnormality may
be present in both.
MND Association Study
Prof. Jackie de Belleroche has been funded by the MND
Association to examine the molecular genetics of Familial
Amyotrophic lateral sclerosis (The medical term for FMND). She
is in contact with over 150 families in the UK with familial MND.
Her research is in two stages:
Contact is made with families where more than one person has
been affected with MND. Blood samples are collected from
affected and unaffected family members and these are used to
prepare DNA.
The DNA samples are then screened to locate the defective gene.
Once the function of the gene has been characterised, we can start
to target treatment either pharmacological or, perhaps in the
future, by gene replacement therapy.

This work is vital to the understan
should help in the understanding i

nding of familial MND and
in all forms of the disease.

Familial Motor Neurone Disease

Genetics

Information about the characteristics of an individual are
contained in a blueprint called DNA sequence (Deoxyribonucleic
acid codes for our components genes- which are organised in pairs
and are passed on to our offspring).
Each parent contributes half their genes at random to their
offspring, providing a different selection or 'mix' of each partner's
genes to each child.
In FMND there is a recorded family history with cases occurring
through different generations. By studying the genetic make-up
of these families scientists are trying to identify this 'genetic
fingerprint' which is not found in the rest of the country
One important development was the identification of the gene
mutation SOD1 which is present in some cases of FMND. This is a
defect in the superoxide dismutase gene, which in healthy people
is thought to have a beneficial detoxifying action. To put this
discovery in context, FMND represents approximately 5-10% of
all cases of MND. Only 15-20% of FMND cases are known to be
related to a mutation in the SOD1 gene, leaving the cause
unknown for 80-85% of familial cases. Therefore this partially
faulty gene accounts for less than 1% of all MND cases.

Genetic Counselling (Written by Dr Christine
Garrett)

We recognise that many families need advice from an expert about
how FMND will affect their family. We have asked Clinical
Geneticist Dr Christine Garrett to give a summary of the type of
service that can be provided if required.
"Although there is a long way to go before we will fully
understand how it is that MND can sometimes run in families, the
underlying genetic change in a few families has been identified

and research in this area is beginning to bear fruit. As with many
genetic diseases, the next decade should provide answers to many
puzzling questions about this condition.
If more than one member of your family has MND, you may be
concerned about developing the condition yourself, or worried
about the chance of the problem being passed on to the next
generation. Many people are unsure about the best way to pass on
information to other members of the family, especially children.
You may have questions about any tests that are available to
predict who might have inherited the disorder.
The discussion of this type of information is termed Genetic
Counselling, and should be available to everyone, as there are
Genetic Counselling clinics throughout the UK. If you would like
to see a genetic counsellor, ask your family doctor to refer you to
your nearest clinic."

Familial Motor Neurone Disease

How can you help the Study?

If more than one member of your family has, or has had MND you
can contact Prof. Jackie de Belleroche. She will take down details
of your family tree and answer any particular questions. Further
information can be sent to your family via Fingerprint a newsletter
written specifically for families with FMND. Then if possible,
blood samples will be requested from appropriate adult members
of your family. The information which these can provide is
invaluable for the future of MND research and to your family.
Support and information is available from Prof. de Belleroche, or
her Support Nurse, Juliet Greenwood
at the following address:

Molecular Neurobiology Group
Department of Neuromuscular Diseases
Imperial College School of Medicine
Charing Cross Hospital Site
Fulham Palace Road
London. W6 8RF
Tel: (020) 88467052- answer machine when
unattended.

OR
contact the MND Association through their web page or on their
helpline 0345 626262