Clinical and Genetic Study of Autism Spectrum Disorder
Condition: Autism
MeSH terms: Autistic Disorder; Autism Spectrum Disorder
Study type: Observational

Summary: 
      The purpose of this study is to prepare instruments for Autism Spectrum Disorder (ASD), to
      collect clinical, neuropsychological, and genetic data of ASD probands and their family, and
      to identify the genetic variants close to etiological genes of ASD in a Taiwanese sample
    

Detailed description: 
      Autism is a pervasive neurodevelopmental disorder with prominent reciprocal social and
      communication impairment and restricted repetitive behavior or interest. Based on the number
      of symptoms and functional impairment, autistic disorder, Asperger disorder, and atypical
      autism (or PDDNOS) are conceptualized as the autism spectrum disorder (ASD). Most recent
      survey estimated the prevalence of narrow diagnosis of autistic disorder to be around 0.1% to
      0.2%, and 0.59 % to 0.63% for ASD, with a four-fold male predominance. Due to high
      heritability (> 0.9), high family recurrence risk (λ = 60), and severe impairment without
      effective prevention and treatment available for ASD, this disastrous disease has been
      prioritized for molecular genetic study from public health perspective. The proposed research
      is the first systematic approach combining clinical and molecular genetic study of ASD
      involving multi-sites and three research cores: assessment core (by Gau SS and Wu YY),
      molecular genetics core (by Chen CH), and data/statistics core (by Gau SS).

      The long-term objective of this study is to establish clinical and genetic database of autism
      and their family for etiology study, exploration of pathogenesis, and developing new
      treatment. The specific aims are:

        1. to establish the psychometric properties of three Chinese versions of rating scales for
           ASD: SCQ, SRS, and ABC;

        2. to collect clinical, neuropsychological, and genetic data of ASD probands and their
           family and

        3. to identify the genetic variants close to etiological genes of ASD in a Taiwanese sample
           using candidate gene case-control association study design (e.g., Neuroligin gene
           family, MeCP2 gene, and FOXP2 gene, parent trio and population-based studies) and whole
           genome linkage analysis for multiplex families.

      After well-preparation of instruments, DNA collection procedure, and assessor's training in
      the first 6 months, we will recruit 40, 170, and 90 ASD families in the first, second, and
      third year of the project, respectively. The instruments include the ADI-R, ADOS, K-SADS-E,
      SCQ, SRS, and ABC for measuring autistic psychopathology; WISC-III, MSEL and PPVT for
      cognitive ability; CPT, CANTAB, and WCST for neuropsychological functioning, and MRI, MRS,
      and DSI for brain imaging study.

      We anticipate the establishment of the database of 300 ASD families, completion of the
      mutation screening of several candidate genes, and determination of their association with
      ASD and its intermediate phenotype in our sample. The identification of susceptible genes for
      ASD would be a major breakthrough in child psychiatry because this revelation would
      facilitate the scientific diagnosis of autism and as a result, it would shed light on the
      pathogenesis of autism and contribute to the development of the novel, specific and effective
      treatment of this devastating disease.
    

Observational model: Family-Based
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        The sample will consist of 300 children and adolescents with ASD, aged 3-18.
      
Biospecimen description: 
      The subjects will receive blood withdrawal. The blood sample will be used for establishing
      lymphoblastoid cell lines, which will be used for molecular genetic experiments.
    
Keywords: autism spectrum disorder; family genetic study; gene; phenotype; endophenotype