Investigation of the HDAC4 Copy Number Variation and Its Effect on Gene and Protein Expression in Patients With ASD

Specific Aims of this study:

1. To understand the distribution of HDAC4 CNV in the families of the ASD patients with HDAC4 CNV;
2. To perform the analysis of gene expression;
3. To investigate the HDAC4 protein level expression;
4. To investigate the correlation of clinical/cognitive features with HDAC4 CNV, RNA and protein expression in ASD patients, and compare with their unaffected family members.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Other: Psychiatric diagnosis

Detailed Description

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting up to 1/50 in the world and 1% in Taiwan. ASD is a clinically and genetically heterogeneous complex disorder with high heritability. Due to its high prevalence, lifetime impairment and no effective prevention and treatment, ASD has been prioritized for molecular genetic study. Among the genetic findings based on our copy number variation (CNV) analysis of 335 patients with ASD, HDAC4 gene is selected to help us understand the pathogenesis of ASD by investigating parent-of-origin and the gene and protein expression of this gene, alongside neurocognitive and behavioral phenotypes.

Based on our findings on HDAC4 CNV analysis, the patients with HDAC4 CNVs (~30 patients) and their families will be invited to participate the investigation of the CNV, RNA and protein expression analysis. Five healthy controls without any diagnosis of psychiatric disorders will be recruited to perform the comparison with ASD patients with HDSC4. The autistic symptoms and behavioral phenotypes assessed by the Chinese SCQ and SRS, and the cognitive function assessed by intelligence test and WCST will be used to reveal the associations among the CNVs, RNA expression, protein level and clinical/cognitive phenotypes.

According to our previous CNV findings at the HDAC4 locus, we expect to find CNV in HDAC4 variation in another independent sample of our ASD cohort and to explore how HDAC4 CNVs affect the RNA and protein expression of HDAC4. We anticipate our endeavors will provide the comprehensive profiles of the CNV, RNA and protein expressions and the clinical features of ASD patients with HDAC4 CNVs and contribute to our understanding of the pathogenesis of ASD.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • National Taiwan Univeristy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

30 ASD patients with HDAC4 CNVs and 5 healthy controls without any diagnosis of psychiatric disorders will be recruited.

Description

Inclusion Criteria:

• ASD group: Subjects who met the diagnostic criteria of either autistic disorder or Asperger's disorder defined by the DSM-IV criteria.

Exclusion Criteria:

• TD group: Subjects with any current or lifetime DSM-IV psychiatric disorders.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ASD group; ASD patients with HDAC4 CNVs	Other: Psychiatric diagnosis
TD group; Typically developing controls without lifetime ASD or a family history of ASD	Other: Psychiatric diagnosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Copy number variation (CNV) analysis	Using SYBR-Green based real-time qPCR (Applied Biosystems, Forster, CA) to detect the CNVs encompassing HDAC4 gene in participants.	5 days

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: September 12, 2018
• First Submitted That Met QC Criteria: September 12, 2018
• First Posted (Actual): September 13, 2018

Study Record Updates

• Last Update Posted (Actual): September 19, 2018
• Last Update Submitted That Met QC Criteria: September 17, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: 201608089RIN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No