Abstract
Autism spectrum disorder (ASD) is a complex neurological disease characterized by impaired social communication and interaction skills, rigid behavior, decreased interest, and repetitive activities. The disease has a high degree of genetic heterogeneity, and the genetic cause of ASD in many autistic individuals is currently unclear. In this study, we report a patient with ASD whose clinical features included social interaction disorder, communication disorder, and repetitive behavior. We examined the patient's genetic variation using whole-exome sequencing technology and found new de novo mutations. After analysis and evaluation, ARRB2 was identified as a candidate gene. To study the potential contribution of the ARRB2 gene to the human brain development and function, we first evaluated the expression profile of this gene in different brain regions and developmental stages. Then, we used weighted gene coexpression network analysis to analyze the associations between ARRB2 and ASD risk genes. Additionally, the spatial conformation and stability of the ARRB2 wild type and mutant proteins were examined by simulations. Then, we further established a mouse model of ASD. The results showed abnormal ARRB2 expression in the mouse ASD model. Our study showed that ARRB2 may be a risk gene for ASD, but the contribution of de novo ARRB2 mutations to ASD is unclear. This information will provide references for the etiology of ASD and aid in the mechanism-based drug development and treatment.
Highlights
Autism spectrum disorder (ASD) is a complex, lifelong, neurodevelopmental disease with a high degree of genetic heterogeneity, characterized by impaired social communication and interaction skills, stereotyped behavior, declining interest, and repetitive activities [1, 2]
We examined a family including a child with ASD and found a new de novo mutation of ARRB2
Blood samples were collected from child with ASD and their parents
Summary
Autism spectrum disorder (ASD) is a complex, lifelong, neurodevelopmental disease with a high degree of genetic heterogeneity, characterized by impaired social communication and interaction skills, stereotyped behavior, declining interest, and repetitive activities [1, 2]. Research indicates that the incidence of ASD in men is 4–5 times that in women, this difference is reduced among individuals with intellectual disabilities [4]. Genetic factors play a key role in the etiology of ASD and are combined with early environmental factors. Studies have shown that the incidence of childhood trauma, self-mutilation, and suicidal behaviors and thoughts of ASD patients is significantly increased [5], resulting in a heavy financial burden on families and society [6]. In the UK, the lifetime cost of ASD patients is £920,000 (US$1.36 million) [7]
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