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Functional implications of pathogenic mutations in synaptic proteins

Most neurodevelopmental disorders (NDDs) have a strong genetic component. Until recently, causal genes had primarily been found in the context of Intellectual Disability (ID). Although twin studies indicate that NDDs such as attention deficit hyperactivity disorder (ADHD) or autism spectrum disorders (ASD) have an important genetic background, classical genetic studies have failed to identify genes with high penetrance in these conditions.

Recent developments in DNA analysis and sequencing, such as next-generation sequencing, SNP arrays, exome sequencing or analysis of copy number variations (CNVs), allow to study the whole genome of large cohorts of affected individuals, enabling the analysis of CNS disorders with highly heterogeneous genetic etiology.

Interestingly, many of the genes identified in the context of NDDs are involved in synaptic function pointing towards a synaptic dysfunction as an important contributing factor in many of these disorders. It is therefore important to understand how these mutations alter normal synaptic biology, specially at the molecular level. Deciphering the molecular pathology of these disorders should path the way for future therapeutical approaches.

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