affects at least one child in every 2 500, mainly boys. Half of these never
learn to speak and three-quarters have mental handicaps, though a small
minority may show an exceptional talent for drawing, music or mental arithmetic.
Although doctors now have a somewhat better understanding of how such individuals
might perceive the outside world, they have yet to identify clearly the
precise underlying brain dysfunction. "We are still only able to observe
the development of the brain or study its functioning in a relatively unsophisticated
way, particularly in young children, which is when autism first shows itself,"
explains Anthony Bailey of the Institute of Psychiatry in London.
Drawings by Lisa Perini shown
at the international exhibition, 'Creation from Silence' (Burgos
- E), organised by the Association of Parents of Autistic Children,
where she won first prize.
For several years now, researchers have adopted a genetic and molecular
approach to try to improve their understanding of the origins of this
disease. Studies carried out on families of autistic people have revealed
certain predisposing factors. In monozygotic twins (genetically identical
and coming from a single fertilised egg), if one child is affected, then
in some 60% of cases the other one is too. In dizygotic twins (genetically
non-identical, from two different eggs), this only occurs in about 4%
of cases, indicating the importance of genetic influences. Studies of
families with twins suggest that these influences might also extend to
Asperger's syndrome and related disorders.
led specialists to search for the few genes that they suspected must underlie
the development of autism. The question was: how many and which ones?
In 1995, in an attempt to identify the culprits, understand the origins
of the disease and - ultimately - develop a treatment, an international
consortium was set up to carry out a study of the molecular genetics of
autism. Coordinated by researchers at the Institute of Psychiatry in London,
it has received EU funding since 1997.(1) "About
200 families is generally considered to be the minimum sample for a study
of this kind. This is far too many for any one country, " explains Dr
Bailey. As virtually no individuals with autism have descendants, the
genetic study has to focus on the relatively small number of families
containing two individuals with autism or a related disorder. Hence the
need for an international approach, and a consortium consisting of British,
Dutch, German, French, Danish, Greek and American clinicians and researchers.
First described by the American Leo Kanner in 1943, autism is a
disorder which affects an individual's complete mental development.
The symptoms (lack of social interaction, communication and imagination;
limited interests and activities, etc.) vary greatly with age. The
only treatment is early specialised education aimed at making the
environment more accessible to the autistic child who may then possibly
acquire language, social skills, learning ability and a knowledge
of the world. Autistic adults, on the other hand, usually have to
live in an adapted medico-social environment unless they can be
cared for by their family. •To find out more about autism: Uta Frith,
Autism: Explaining the Enigma, Basil Blackwell, Oxford, 1989.
This computer image of a gel shows the markers from several families
with autism, each marker being labelled with a different fluorescent
dye. The gel shows where the markers shared between individuals
vary; this data will help to pinpoint the genes responsible.
Once the families had been identified and autism diagnosed, a blood sample
was taken from each individual. Some of each sample was used to extract
the DNA and to carry out the first molecular genetics studies in the laboratory
of Professor Anthony Monaco at The Wellcome Trust Centre for Human Genetics
in Oxford. The remainder was used to establish permanent cultures of cell
lines. Kept in a cell bank, these cultures enable all the research teams
to work on the same subjects. They also make it possible to carry out
any additional analyses which may prove necessary.
stage, before the molecular biologists are brought in, is aimed at establishing
a precise diagnosis and excluding subjects in whom autism is associated
with a recognisable medical disorder that might distort the results. It
is important to reliably quantify clinical heterogeneity in autism in
order to be able to establish a link between the variability of the illness
and the precise genes involved.
partners concentrated much of their efforts on this strategic aspect of
selecting their subjects. They met regularly for working seminars on the
use and reliability of their diagnostic tools and for in-depth discussions
on problematic cases, based in particular on video recordings made during
assessments of some patients.
In 1998 - well ahead of schedule - this concerted effort to achieve precise
diagnoses enabled the consortium to publish the first genetic study of
autism ever carried out on a full genome.(2) This
was based on 99 families, including 87 pairs of siblings and 12 families
with more distant relationships (cousins, etc.).
of more than 300 genetic markers distributed at regular intervals across
the full genome (and corresponding to regions which are in principle very
variable from one individual to another), revealed six chromosomes (4,
7, 10, 16, 19 and 22) on which certain sites showed greater similarities
among pairs of autistic individuals than would normally be expected. Two
particularly significant regions were located on chromosomes 7 and 16.
The region identified on chromosome 7 currently looks the most promising,
as it shows the greatest similarities and also contains a number of genes
involved in brain development and function.
To date, more than 130 families have been recruited for the purposes of
this study. The researchers are concentrating their genetic analyses on
the first regions identified as those being potentially linked to the
development of autism. These links must be confirmed by other groups and
the target areas refined to identify the gene(s) involved in each region.
"The identification of these various susceptibility genes is just the
first stage in understanding the development of the disease," concludes
Dr Bailey. "This approach does, however, hold out the hope that we can
begin to give a meaning to a whole set of biological data, with the prospect
that this work will lead to the development of preventative approaches
or specific treatments. This research also raises the possibility of identifying
any non-genetic factors which, in the case of a subject prone to autism,
may lead to either a moderate or severe form of the disease. Although
we still have a long way to go before we achieve our goal, it does seem
closer now than it has ever been."
Through a concerted action (Molecular Genetic Study of Autism - BMH4-CT-97-2759
) under the Biomed 2 programme.
(2) A full genome screen for autism with evidence for linkage to a region
on chromosome 7q, International Molecular Genetic Study of Autism Consortium,
Human Molecular Genetics, 1998, Vol 7, n°3, 571-578