Functional characterization of polymorphisms in 3’untraslated regions of autism-linked genes: role of miRNA-mediated control and splicing in the physiopathology of autism - Joint Project 2014

Starting date
November 1, 2014
Duration (months)
Neurosciences, Biomedicine and Movement Sciences
Managers or local contacts
Lievens Patricia

Autism is characterized by DEFICITS IN VERBAL COMMUNICATION and social interaction. Modulatory factors such as genetic variations in autism-linked genes may contribute to the pathogenesis and to the “nuances” of the phenotypes. Genetic variations in protein-coding DNA (<5% of the genome) did not explain the pathogenesis of autism. For example, Genome Wide Association Studies (GWAS) identified several genes, such as FOXP gene subfamily (including FOXP2 the “LANGUAGE GENE”) that are potentially linked to the verbal deficits observed in autism. However, these studies FAILED to demonstrate that genetic variations in protein coding regions of these genes could play a significant role to the onset of the verbal deficits observed in autism. On the other hand, accumulating data on microRNAs, and other post-transcriptional control elements in the 3’untranslated regions (3’UTRs) of mRNAs, demonstrated the involvement of additional control layers in the physiopathology of human diseases such as cancer and neurodevelopmental disorders. THESE CONTROL LAYERS HAVE NOT BEEN adequately EXPLORED IN AUTISM and therefore their impact might be underestimated. WE HAVE SHOWN THAT variations occurring in miRNAs and their target sites are involved in cancer (Naccarati et al 2012, Pardini et al 2013), and that miRNAs control the expression of Foxp2 (Clovis et al 2012), Foxp1 and potentially other autism related genes. WE HYPOTHESIZE that variations in 3'UTR of autism-related genes (such as FOXP2/Pl) might contribute to the verbal deficits observed in autism. By focusing on genetic variations in 3’UTR of autism-linked genes, WE WILL IDENTIFY THE OCCURRENCE OF THESE VARIATIONS IN AUTISM PATIENTS affected by different degrees of verbal deficits. Next, we will perform functional validation to identify the molecular relevance of these variations in human neurons. The proposed exploratory study could set the stage for the direct investigation of similar variations in additional disease-linked genes.

NOME ENTE FINANZIATORE: Università degli Studi di Verona
IMPORTO: 37.000,00 €
PARTNER ESTERNO: Fondazione Istituto Italiano di Tecnologia


Dipartimento di Scienze Neurologiche, Biomediche e del Movimento
Funds: assigned and managed by the department
Fondazione Istituto Italiano di Tecnologia
Funds: assigned and managed by the department

Project participants

Patricia Lievens
Associate Professor

Collaboratori esterni

Davide De Pietri Tonelli
Fondazione Istituto Italiano di Tecnologia


Research facilities