EU-AIMS synaptic gene deficit project
Research type
Research Study
Full title
Comprehensive characterisation of children and adults with synaptic gene deficits (including Phelan-McDermid Syndrome) and typically developing chidren
IRAS ID
174001
Contact name
Eva Loth
Contact email
Sponsor organisation
King's College London
Duration of Study in the UK
2 years, 6 months, 30 days
Research summary
Autism Spectrum Disorders (ASD) are a group of early onset neurodevelopmental disorders with a strong genetic basis, behaviourally defined based on deficits in social communication and repetitive and restricted behaviours and interests. To date, medical treatments that help individuals to significantly improve their outcome are largely lacking.
The discovery of effective treatments has been a challenge because ASD are phenotypically, etiologically and genetically very heterogeneous, and the underlying pathophysiology(ies) remains poorly understood. However, the recent identification of monogenic forms of ASD offers novel opportunities for the understanding of pathophysiological mechanisms. Many ASD risk genes, including genes encoding for cell adhesion molecules (e.g., NRXNs, Nlgns) and postsynaptic scaffolding proteins (SHANK family) affect synaptic plasticity, and may disturb the balance between excitatory and inhibitory currents and brain connectivity. Comprehensive multilevel characterisation of volunteers carrying these risk genes may help to identify biomarkers related to synaptic defects and their link to behavioural and clinical abnormalities. The aim of this project is to comprehensively phenotype and genotype approximately 40 to 50 children and adults with a SHANK3 deletion syndrome PhelanMcDermid Syndrome (PMS) and approximately 40 carriers of other synaptic or neurodevelopmental CNVs linked to ASD (including NRXN1, 16p11.2, 22q11.12). Study participation includes parentreport online questionnaires (completed at home) and two visits to the Institute of Psychiatry, King’s College London. We will create a comprehensive profile of each proband including ASD symptoms and neurodevelopmental/ neuropsychiatric comorbidities, IQ, level of adaptive behaviour, neurocognition, brain structure and function, biochemistry, and genomic characterisation. We also aim to phenotype (using a lighter protocol) and genotype both biological parents (and, where applicable, siblings) to explore the effect of family background on phenotypic variability. In addition, we aim to recruit N=30 children, adolescents and young adults with “idiopathic” ASD and N=30 typically developing children to serve as further comparison groups.
REC name
London - Queen Square Research Ethics Committee
REC reference
15/LO/0305
Date of REC Opinion
27 Mar 2015
REC opinion
Further Information Favourable Opinion