Abstract
Autism Spectrum Disorders (ASDs) is a multigenic and multifactorial neurodevelopmental group of disorders diagnosed in early childhood, leading to deficits in social interaction, verbal and non-verbal communication and characterized by restricted and repetitive behaviors and interests. To date, genetic, descriptive and mechanistic aspects of the ASDs have been investigated using mouse models and post-mortem brain tissue. More recently, the technology to generate stem cells from patients' samples has brought a new avenue for modeling ASD through 2D and 3D neuronal models that are derived from a patient's own cells, with the goal of building new therapeutic strategies for treating ASDs. This review analyses how studies performed on mouse models and human samples can complement each other, advancing our current knowledge into the pathophysiology of the ASDs. Regardless of the genetic and phenotypic heterogeneities of ASDs, convergent information regarding the molecular and cellular mechanisms involved in these disorders can be extracted from these models. Thus, considering the complexities of these disorders, patient-derived models have immense potential to elucidate molecular deregulations that contributed to the different autistic phenotypes. Through these direct investigations with the human in vitro models, they offer the potential for opening new therapeutic avenues that can be translated into the clinic.
Highlights
GENETICS OF AUTISMAutism is a complex, multigenic and multifactorial neurodevelopmental disorder that was originally defined based on three clinical criteria (i) abnormalities in social interactions, (ii) deficits in verbal and non-verbal communication and (iii) the presence of stereotypical and repetitive behaviors [1]
This review aims to discuss the strengths and limitations of mouse models, human post-mortem brain tissue and induced pluripotent stem cells (iPSCs) in studying Autism Spectrum Disorders (ASDs), and to summarize how these studies combined have contributed to advance our understanding into the molecular and cellular mechanisms that potentially cause ASDs
The current review aims to bring together findings in the field of ASDs provided by genetics, mouse models, postmortem brain studies and iPSC-derived studies
Summary
GENETICS OF AUTISMAutism is a complex, multigenic and multifactorial neurodevelopmental disorder that was originally defined based on three clinical criteria (i) abnormalities in social interactions, (ii) deficits in verbal and non-verbal communication and (iii) the presence of stereotypical and repetitive behaviors [1]. Syndromic forms of autism such as Fragile X [9] or Rett syndromes [10] along with Tuberous sclerosis [11] and others (see Table 1) are characterized by a specific set of clinical features as well as the autistic triad They are often monogenic, genetically well characterized and account for 10–20% of ASDs’ cases [18]. Examples of specific set of clinical features that can be seen in the syndromic ASDs include facial dysmorphisms, epilepsy, intellectual disability, and systemic manifestations. These features are not observed in nonsyndromic forms of autism [2]
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