Key role for gene dosage and synaptic homeostasis in autism spectrum disorders

Roberto Toro (1) , Marina Konyukh (1) , Richard Delorme (1, 2, 3) , Claire Leblond (1) , Pauline Chaste (1, 2) , Fabien Fauchereau (1, 4) , Mary Coleman (5) , Marion Leboyer (6, 3) , Christopher Gillberg (7, 8) , Thomas Bourgeron (1, 4, 3)

1 Génétique Humaine et Fonctions Cognitives
2 AP-HP Hôpital universitaire Robert-Debré [Paris]
3 Fondation FondaMental [Créteil]
4 UPD7 - Université Paris Diderot - Paris 7
5 Foundation for Autism Research
6 IMRB - Institut Mondor de Recherche Biomédicale
7 GU - Göteborgs Universitet
8 Institute of Child Health [London]

Autism spectrum disorders (ASD) are characterized by impairments in reciprocal social communication, and repetitive, stereotyped verbal and non-verbal behaviors. Genetic studies have provided a relatively large number of genes that constitute a comprehensive framework to better understand this complex and heterogeneous syndrome. Based on the most robust findings, three observations can be made. First, genetic contributions to ASD are highly heterogeneous and most probably involve a combination of alleles with low and high penetrance. Second, the majority of the mutations apparently affect a single allele, suggesting a key role for gene dosage in susceptibility to ASD. Finally, the broad expression and function of the causative genes suggest that alteration of synaptic homeostasis could be a common biological process associated with ASD. Understanding the mechanisms that regulate synaptic homeostasis should shed new light on the causes of ASD and could provide a means to modulate the severity of the symptoms.

Domains: Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]

Roberto Toro, Marina Konyukh, Richard Delorme, Claire Leblond, Pauline Chaste, et al.. Key role for gene dosage and synaptic homeostasis in autism spectrum disorders. Trends in Genetics, 2010, 26 (8), pp.363-372. ⟨10.1016/j.tig.2010.05.007⟩. ⟨pasteur-01967134⟩