The study group identified a serious mutation of the SYN1 gene on the X chromosome of the members of a French-Canadian family, affected by epilepsy associated with autism. Through a further analysis on patients affected by autism or epilepsy, other mutations of the same gene have been identified respectively in 1% of the autistic patients and 3,5% of the epileptic patients, demonstrating the key role of SYN 1 in the genetic predisposition to the two pathologies."The results of this study - declares Prof. Fabio Benfenati - are fundamental for two reasons. The first is that they demonstrate that the two pathologies have a common genetic basis. The second, because they allow to hypothesise the pathogenic role of a dysregulation of synaptic homeostasis, which is the basis for the regulation of excitability and the cognitive processes".In fact, Synapsin-1 is a protein which exercises complex roles in neuronal development and synaptic plasticity. The researchers have discovered that the Synapsin-1 mutations which cause epilepsy and autism, cause variations in the release of neurotransmitter with a consequent loss of the equilibrium between excitability and inhibition necessary for the correct functioning and development of the brain.
"Our data demonstrated that - continues Dr. Fassio, first author of the work - the defects in the regulation of the synaptic vesicle cycle could be a common molecular mechanism in the two pathologies, opening a new way for the study of new therapies".
Epilepsy and autism coexist in about 20% of patients and the identification of common genetic traits allows to study the molecular mechanisms implicated in both pathologies, which is a necessary step for the development of innovative therapies. The period in which the two pathologies appear coincides with the one in which the neuronal circuits remodel on the basis of the acquisition of experiences: this suggests a possible common mechanism at their basis. Both the epileptic seizures and the behavioral defects of autism are manifestations of anomalies present at the level of the cortical circuits. Thus, the necessity of understanding of the role of the genes that codify for the proteins involved in neural development and synaptic plasticity is emerging strongly.
"It had already been observed that nearly one third of the patients affected by different kinds of autism also develop epileptic attacks and, vice versa, in the gravest forms of epilepsy associated to mental retardation, often autistic traits are present. - declares Prof. Patrick Cossette - This has been confirmed by the fact that, in the family we studied, all the male carriers of the genetic mutation of SYN1 were affected by epilepsy but, often, there were also present typical traits of learning and behavioural difficulties, typical of Autistic Spectrum Disorders. Our work identifies a possible cause at the basis of this interrelation".
This study, in which Prof. Flavia Valtorta of the University Vita-Salute San Raffaele of Milan participated, has been possible thanks to the Fondazione Telethon and Compagnia di San Paolo and has been sponsored by the Italy-Quebec Bilateral Scientific and Technological Programme of the Italian Ministry of Foreign Affairs.