Press release

TWO GENES IDENTIFIED AS ASSOCIATED WITH AUTISM

Two genes associated with autism, in two families where several members are affected, were revealed by French and Swedish researchers at the Institut Pasteur, INSERM, psychiatric departments in Paris (Créteil University Hospital and the Robert Debré public hospital) and the psychiatric department of the University of Göteborg. This is the first time that genetic mutations have been precisely identified in individuals with autism. These results are published as a preview on the web site belonging to the magazine Nature Genetics.

For several years now, a considerable amount of research has been carried on the genetics of autism. A large number of parts in the genome were suspected and possible genes were incriminated, without any of them being unquestionably associated with the autistic syndrome. It is now an established fact thanks to a study conducted by Thomas Bourgeron's team at the Institut Pasteur (Inserm 21 team "functional genomics and development", University of Paris VII) in collaboration with Marion Leboyer (Inserm 513 Unit "neurobiology and psychiatry ", University of Paris XII, Créteil University hospital) and Christopher Gillberg from the Göteborg University hospital in Sweden. In two different families, they identified mutations altering two genes on the X chromosome and which seem to be implicated in the formation of synapses (communication spaces between neurons).

A genetic mutation on the NLGN4 gene was revealed in a family where two boys were affected, one with autism and the other with Asperger Syndrome (AS)¹. The mutation prevents a complete protein from forming.
In another family, which also has two brothers affected, one with autism and the other with AS, a mutation of the NGLN3 gene, also inherited from the mother, has been identified.

The alteration of NLGN3 or NLGN4 may assign certain essential synapses to the processes of deficient communication in people presenting autistic disorders. As a matter of fact, these genes code for the cell-adhesion proteins located at synapses level, which suggests that a defect in the formation of synapses could create a predisposition to autism.

NLGN4 and NLGN3 are located in the X chromosome regions that had been associated with autism in other studies, one of which was the collaborative study Paris Autism Research International Sib-Pair Study (PARIS) coordinated by Marion Leboyer and Christopher Gillberg.

Autism is a complex syndrome classified among pervasive development disorders. It is characterised by impairements in social interactions and communication, associated with restricted, repetitive and stereotyped behaviours, which appears before the age of 3 years. It is today considered that one in 1,000 children is affected by autism, and it is observed four times more often in boys than girls.
Various observations are in favour of a genetic predisposition to autism. The risk of autism recurring in families affected is 45 times higher than in the general population. Furthermore, epidemiological studies conducted on monozygotic twins show that when one of the children is affected by autism, the probability of the second also being autistic is 60%, while this risk is almost inexistent in dizygotic twins. The increased risk between siblings and the twin studies indicate the presence of susceptibility genes to autism. But it is highly probable that several genes are implicated and that, moreover, susceptibility genes may vary from one family to another.

If the genes now identified are however not the sole and unique genes in autism, this study nevertheless opens new areas for research so that this complex and heterogeneous syndrome which is autism may be better understood.

This study was conducted with the support of the Délégation à la Recherche Clinique de l'AP-HP (public hospitals' Clinical Research Delegation), the ACI young researchers from the Ministry for Research, the France Telecom Foundation for research into autism, and the Fondation de France.

1 Patients who are affected by this syndrome have better cognitive performances and a better aptitude for language than patients affected with other forms of autism.

Sources:

- "Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism" Nature Genetics - May 2003
Stéphane Jamain (1), Hélène Quach (1), Catalina Betancur (2), Maria Rastam (3), Catherine Colineaux (2,4), I. Carina Gillberg (3), Henrik Söderström (3), Bruno Giros (2), Marion Leboyer (2,5), Christopher Gillberg (3,6), Thomas Bourgeron (1), & the PARIS study (7)

1 Human Immunogenetics Laboratory, INSERM 21 team, University of Paris 7, Institut Pasteur, Paris (FRANCE).
2 INSERM 513 Unit, Faculty of Medicine, University of Paris XII, Créteil (FRANCE)
3 Department of Child and Adolescent Psychiatry, Göteborg University, (SWEDEN)
4 Department of Psychiatry for the Child and the Adolescent, Robert Debré Hospital, Paris (FRANCE).
5 Psychiatric Department, Albert Chenevier and Henri Mondor Hospital, Créteil (FRANCE).
6 Saint George's Hospital Medical School, London, (UK).
7 Paris Autism Research International Sib-pair Study (FRANCE).

This article is on-line on the Nature Genetics site: http://www.nature.com/ng/

Contacts :

- Clinical: Marion LEBOYER - Tel: +33 (0) 149.81.30.51 - Email: leboyer@im3.inserm.fr
- Scientific: Thomas BOURGERON - Tel: +33 (0) 140.61.32.16 - Email: thomasb@pasteur.fr
- Institut Pasteur - Press Office - Tel: +33 (0) 145.68.81.46 - Email: presse@pasteur.fr
- INSERM - Press Office - Tel: +33 (0) 144.23.60.86 / 97 - Email: presse@tolbiac.fr