Clinical and Genetic Study of Autism Spectrum Disorder

NCT ID: NCT00494754

Last Updated: 2021-05-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2011-04-30

Brief 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.

Conditions

Autism

Study Design

• Observational Model Type: FAMILY_BASED
• Study Time Perspective: OTHER

Eligibility Criteria

Inclusion Criteria

1. subjects have a clinical diagnosis of autistic disorder, Asperger disorder, or atypical autism defined by the DSM-IV and ICD-10, which was made by a full-time board-certificated child psychiatrist at the first visit and following visits;

2. their ages range from 3 to 18 when we conduct the study;

3. subjects have at least one biological parent;

4. both parents are Han Chinese; and (5) subjects and their biological parents (and siblings if any) consent to participate in this study for complete phenotype assessments and blood withdraw for genetic study

Exclusion Criteria

1. if they currently meet criteria or have a history of the following condition as defined by DSM-IV: Schizophrenia, Schizoaffective Disorder, or Organic Psychosis.

2. if they completely cannot cooperate with blood withdrawal, collection of saliva, or buccal swabs.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Science and Technology Council, Taiwan

OTHER_GOV

Sponsor Role: collaborator

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan Shur-Fen Gau, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dept of Psychiatry, National Taiwan University Hospital

Locations

National Taiwan University Hospital

Taipei, , Taiwan

Taipei City Psychiatric Center

Taipei, , Taiwan

Chang Gung Children's Hospital

Taoyuan District, , Taiwan

Taoyuan Mental Hospital

Taoyuan District, , Taiwan

Countries

Taiwan

References

Chien YL, Chen YC, Chiu YN, Tsai WC, Gau SS. A translational exploration of the effects of WNT2 variants on altered cortical structures in autism spectrum disorder. J Psychiatry Neurosci. 2021 Dec 3;46(6):E647-E658. doi: 10.1503/jpn.210022. Print 2021 Nov-Dec.

Reference Type: DERIVED

PMID: 34862305 (View on PubMed)

Chien YL, Wu YY, Chen HI, Tsai WC, Chiu YN, Liu SK, Gau SS. The central nervous system patterning gene variants associated with clinical symptom severity of autism spectrum disorders. J Formos Med Assoc. 2017 Oct;116(10):755-764. doi: 10.1016/j.jfma.2016.11.015. Epub 2017 Jan 9.

Reference Type: DERIVED

PMID: 28081867 (View on PubMed)

Yin CL, Chen HI, Li LH, Chien YL, Liao HM, Chou MC, Chou WJ, Tsai WC, Chiu YN, Wu YY, Lo CZ, Wu JY, Chen YT, Gau SS. Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder. Mol Autism. 2016 Apr 1;7:23. doi: 10.1186/s13229-016-0087-7. eCollection 2016.

Reference Type: DERIVED

PMID: 27042285 (View on PubMed)

Chiu YN, Chou MC, Lee JC, Wong CC, Chou WJ, Wu YY, Chien YL, Gau SS. Determinants of maternal satisfaction with diagnosis disclosure of autism. J Formos Med Assoc. 2014 Aug;113(8):540-8. doi: 10.1016/j.jfma.2012.07.040. Epub 2012 Nov 6.

Reference Type: DERIVED

PMID: 25037759 (View on PubMed)

Chen CH, Huang CC, Cheng MC, Chiu YN, Tsai WC, Wu YY, Liu SK, Gau SS. Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders. Mol Autism. 2014 Jun 25;5:36. doi: 10.1186/2040-2392-5-36. eCollection 2014.

Reference Type: DERIVED

PMID: 24999380 (View on PubMed)

Lau WY, Gau SS, Chiu YN, Wu YY. Autistic traits in couple dyads as a predictor of anxiety spectrum symptoms. J Autism Dev Disord. 2014 Nov;44(11):2949-63. doi: 10.1007/s10803-014-2151-5.

Reference Type: DERIVED

PMID: 24907095 (View on PubMed)

Chien WH, Gau SS, Liao HM, Chiu YN, Wu YY, Huang YS, Tsai WC, Tsai HM, Chen CH. Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders. Mol Autism. 2013 Aug 1;4(1):26. doi: 10.1186/2040-2392-4-26.

Reference Type: DERIVED

PMID: 23915500 (View on PubMed)

Chien WH, Gau SS, Chen CH, Tsai WC, Wu YY, Chen PH, Shang CY, Chen CH. Increased gene expression of FOXP1 in patients with autism spectrum disorders. Mol Autism. 2013 Jul 1;4(1):23. doi: 10.1186/2040-2392-4-23.

Reference Type: DERIVED

PMID: 23815876 (View on PubMed)

Lin PI, Chien YL, Wu YY, Chen CH, Gau SS, Huang YS, Liu SK, Tsai WC, Chiu YN. The WNT2 gene polymorphism associated with speech delay inherent to autism. Res Dev Disabil. 2012 Sep-Oct;33(5):1533-40. doi: 10.1016/j.ridd.2012.03.004. Epub 2012 Apr 21.

Reference Type: DERIVED

PMID: 22522212 (View on PubMed)

Chien YL, Wu YY, Chen CH, Gau SS, Huang YS, Chien WH, Hu FC, Chao YL. Association of HLA-DRB1 alleles and neuropsychological function in autism. Psychiatr Genet. 2012 Feb;22(1):46-9. doi: 10.1097/YPG.0b013e32834915ae.

Reference Type: DERIVED

PMID: 21716163 (View on PubMed)

Other Identifiers

9561709027

Identifier Type: -

Identifier Source: org_study_id