Customized gene therapies for autism spectrum disorders caused by monogenic mutations

Mutation in multiple genes were already described to be contributing to autism spectrum disorder. Although it is hard to make a defined prognosis, it is plausible that early detection of such mutations might allow to design a gene-therapy, tailored specifically for a given individual, and, consequently, to compensate the mutation and cure the symptoms. Some genes, mutations in which are likely to contribute to autism spectrum disorders (ASDs), are discussed below.Due to vast variety of mutations leading to ASDs, personalized CRISPR-Cas9 mediated genome editing approaches are regarded as a promising way to combat these disorders.

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ADNP

The ADNP gene (Activity-Dependent Neuroprotective Protein) plays a significant role in brain development and function. Mutations in this gene are associated with autism spectrum disorder and intellectual disabilities. ADNP is crucial for neurodevelopmental processes, including neuron formation, differentiation, and synapse formation. It regulates the expression of various genes involved in neural activity and brain structure maintenance. ADNP mutations can lead to altered brain connectivity and function, contributing to the clinical manifestations of autism, such as impaired social interactions, communication difficulties, and repetitive behaviors. Additionally, ADNP influences microtubule dynamics, essential for neuronal structure and transport, further impacting neurodevelopmental outcomes.

ANKRD11
The ANKRD11 gene (Ankyrin Repeat Domain-Containing Protein 11) is implicated in neurodevelopment and associated with autism spectrum disorder and KBG syndrome. ANKRD11 plays a critical role in regulating gene expression during brain development by interacting with chromatin and modifying histones, which affects the transcription of multiple genes involved in neuronal function and development.
Mutations in ANKRD11 can disrupt these regulatory processes, leading to abnormalities in brain structure ...
ARID1B
The ARID1B gene (AT-rich interactive domain-containing protein 1B) is crucial for neurodevelopment and is associated with autism spectrum disorder and Coffin-Siris syndrome. ARID1B encodes a subunit of the SWI/SNF chromatin remodeling complex, which regulates the accessibility of DNA to transcription factors and, consequently, gene expression.
Mutations in ARID1B disrupt chromatin remodeling, leading to altered transcription...
ACTL6B
The ACTL6B gene (Actin-Like 6B) is critical for neurodevelopment and has been associated with autism spectrum disorder and intellectual disabilities. ACTL6B encodes a component of the BAF (BRG1/brm-associated factor) chromatin remodeling complex, which regulates the accessibility of DNA to transcription factors, thereby influencing gene expression.
Mutations in ACTL6B disrupt the function of the BAF complex, leading to altered transcription of genes essential for brain development and neuronal function.
AHDC1
The AHDC1 gene (AT-Hook DNA Binding Motif Containing 1) plays a crucial role in neurodevelopment and is associated with Xia-Gibbs syndrome, a condition that often includes autism spectrum disorder features. AHDC1 encodes a protein involved in DNA binding and gene regulation, influencing the expression of genes essential for brain development and function.