Untangle the Multi-Facet Functions of Auts2 as an Entry Point to Understand Neurodevelopmental Disorders.

Neurodevelopmental disorders are psychiatric diseases that are usually first diagnosed in infancy, childhood and adolescence. Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by core symptoms including impaired social communication, cognitive rigidity and repetitive behavior, accompanied by a wide range of comorbidities such as intellectual disability (ID) and dysmorphisms. While the cause remains largely unknown, genetic, epigenetic, and environmental factors are believed to contribute toward the onset of the disease. Autism Susceptibility Candidate 2 (Auts2) is a gene highly associated with ID and ASD. Therefore, understanding the function of Auts2 gene can provide a unique entry point to untangle the complex neuronal phenotypes of neurodevelpmental disorders. In this review, we discuss the recent discoveries regarding the molecular and cellular functions of Auts2. Auts2 was shown to be a key-regulator of transcriptional network and a mediator of epigenetic regulation in neurodevelopment, the latter potentially providing a link for the neuronal changes of ASD upon environmental risk-factor exposure. In addition, Auts2 could synchronize the balance between excitation and inhibition through regulating the number of excitatory synapses. Cytoplasmic Auts2 could join the fine-tuning of actin dynamics during neuronal migration and neuritogenesis. Furthermore, Auts2 was expressed in developing mouse and human brain regions such as the frontal cortex, dorsal thalamus, and hippocampus, which have been implicated in the impaired cognitive and social function of ASD. Taken together, a comprehensive understanding of Auts2 functions can give deep insights into the cause of the heterogenous manifestation of neurodevelopmental disorders such as ASD.

A Neurodevelopmental Perspective for Autism-Associated Gene Function.

Large-scale genetic sequencing studies have identified a wealth of genes in which mutations are associated with autism spectrum disorder (ASD). Understanding the biological function of these genes sheds light onto the neurodevelopmental basis of ASD. To this end, we defined functional categories representing brain development - (1) Cell Division and Survival, (2) Cell Migration and Differentiation, (3) Neuronal Morphological Elaboration, (4) Development and Regulation of Cellular Excitability, and (5) Synapse Formation and Function - and place 100 high confidence ASD-associated genes yielding at least 50 published PubMed articles into these categories based on keyword searches. We compare the categorization of ASD genes to genes associated with developmental delay (DD) and systematically review the published literature on the function of these genes. We find evidence that ASD-associated genes have important functions that span the neurodevelopmental continuum. Further, examining the temporal expression pattern of these genes using the BrainSpan Atlas of the Developing Human Brain supports their function across development. Thus, our analyses and review of literature on ASD gene function support a model whereby differences in brain development - from very early stages of macroarchitectural patterning to late stages of activity-dependent sculpting of synaptic connectivity - may lead to ASD. It will be important to keep investigating potential points of mechanistic convergence which could explain a common pathophysiological basis of ASD behind this disparate array of genes.

Risk factor for children with autism during perinatal period / 中国综合临床

Objective To compare the risk factor of chilldren with autism and ordinary children during perinatal period. Methods One hundred and fourty children with autism and 82 ordinary children were reviewed by self-written general circumstance questionnaire and risk factor questionnaire. Results Viral influenza during pregnancy (x2 =15.29) ,bom suffocate( x2 =6. 04) , premature delivery (x2 =6. 48) , dystocia (x2 =2. 83) and artificial feeding ( x2 = 6. 02 ) were risk factors for children autism (P < 0. 05 ). Conclusion Childeren autism is associated with risk factors in rinatal period. Early dectecion and early prevention and treatment may improve the outcome.