Association between SNAP25 gene polymorphisms and autism spectrum disorder: functional consequences and identification of a possible endophenotype

Autism spectrum disorder (ASD) includes a range of conditions (the “spectrum”) characterized by early onset of severe delay and deviance in the development of social and communicative and unusual response to the environment (repetitive behaviors, difficulties with change, and unusual sensitivity to the inanimate environment). In Diagnostic and Statistical Manual of Mental Disorders (DSM-5), criteria are included for ASD: the previously used triad of impairments in social interaction, communication, and repetitive and restricted interests/behaviors was collapsed into two domains: social communication and restricted and repetitive behaviors. It is now believed that ASD is a result of complex gene–environment interactions, with strong and clear genetic influences: it is currently estimated that over 50% of the risk of developing ASD is attributed to genetic variation. However, ASD has been relatively resistant to classification into more homogeneous clinical or pathological subgroups. The extreme heterogeneity of ASD further complicates our understanding of its biology. The very concept of an autism spectrum acknowledges the fact that clinical phenotypes (including core phenotypes, such as social function and mental flexibility, and associated phenotypes, such as language delay and IQ) of ASD patients can vary dramatically. ASD on a genetic level is arguably even more complicated. Recent evidences suggested that SNAP-25 (synaptosomal-associated protein of 25 kDa) is involved in different neuropsychiatric and neurological disorders. Polymorphisms in the SNAP25 gene as well as altered expression of the protein have been associated with abnormal behavioural phenotype in both animal models and humans. Polymorphisms in the SNAP25 gene have been found in patients affected by attention-deficit/hyperactivity disorder (ADHD), schizophrenia and autism spectrum disorders (ASDs). In an attempt to understand more in depth the role of SNAP-25 in human diseases characterized by an abnormal cognitive profile, we first analysed several SNAP-25 gene polymorphisms in a clinically characterized cohort of children affected by ASD. In particular, we evaluated possible associations between such SNPs and the clinical outcome of ASD. The goal of the present study was to obtain supportive evidence for association between SNAP25 gene and ASD-specific score, in order to identify an endophenotype characterized by specific clinical features and to evaluate a possible overlapping with other neuropsychiatric disorders.

Associazione tra il polimorfismo del gene SNAP25 e i disturbi dello spettro autistico: conseguenze funzionali e identificazione di un possibile endofenotipo