Exome Sequencing in Autistic Spectrum Disorder

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01059201
First received: January 28, 2010
Last updated: July 18, 2014
Last verified: June 2014
  Purpose

Background:

  • Research into the genetic causes of autism spectrum disorder (ASD) involves studies of the DNA of children with autism. New DNA sequencing technology allows researchers to study specific genes in search of genetic changes that may cause or contribute to ASD. Individuals who donated DNA to the Autism Genetic Resource Exchange may benefit from further study of their DNA samples with more advanced DNA sequencing technology.
  • The role of cholesterol in individuals with ASD is currently under investigation. Research has suggested that abnormal cholesterol levels in children with autism may be related to genetic mutations or changes in how cholesterol is regulated in the body.

Objectives:

- To study existing blood samples of children with autism spectrum disorders to evaluate the relationship between genetic traits and cholesterol function.

Eligibility:

- Children with ASD who donated blood samples to the Autism Genetic Resource Exchange.

Design:

- Parents/guardians of minor children with ASD will provide consent for further research to be performed on existing DNA samples in the Autism Genetic Research Exchange databank. Information from this research may be provided to the consenting parents/guardians on a case by case basis, as directed by the researchers.


Condition
Autism Spectrum Disorder
Autism
Autistic Disorder

Study Type: Observational
Official Title: Exome Sequencing in Autistic Spectrum Disorder Patients With Altered Cholesterol Homeostasis

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 322
Study Start Date: January 2010
Detailed Description:

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by functional deficits in three domains: social interaction, communication, and stereotypic behavior. Prevalence has been estimated to be approximately 1/166 children and the public health impact is significant. ASD clearly has a genetic component; however, identification of specific etiologies has been complicated by the heterogeneous nature of ASD. One approach to minimize this problem is to define endophenotypes that can subcategorize ASD patients. Based on our work with Smith-Lemli-Opitz syndrome, we have investigated whether alterations in cholesterol homeostasis may contribute to ASD. We found in 200 ASD subjects that 23% of subjects had serum cholesterol levels less than or equal to 2.28th centile and 9% had levels greater than or equal to 97.72nd centile. Analysis of the sterol profile suggested that the hypocholesterolemia was due to a synthetic defect rather than decreased oral intake. Thus we hypothesize that ASD patients with abnormal cholesterol levels will have polymorphisms or mutations of either genes involved in cholesterol homeostasis or genes encoding proteins whose function is altered by changes in cholesterol levels. To test this hypothesis we propose to 1) use serum cholesterol levels to define ASD endophenotypes and 2) to perform genomic resequencing of all known exons in hypo- and normocholesterolemic ASD patients.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

    1. Prior participation in Autism Genetic Research Exchange
    2. Multiple affected children with ASD
    3. Willingness to contact the NIH and reconsent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01059201

Locations
United States, Maryland
Kennedy Krieger Institute
Baltimore, Maryland, United States, 21205
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210-1240
Sponsors and Collaborators
Investigators
Principal Investigator: Forbes D Porter, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01059201     History of Changes
Other Study ID Numbers: 100022, 10-CH-0022
Study First Received: January 28, 2010
Last Updated: July 18, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Autism Spectrum Disorder
Cholesterol
Exome Sequencing
Autistic Spectrum Disorder
ASD

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Mental Disorders Diagnosed in Childhood
Mental Disorders

ClinicalTrials.gov processed this record on July 24, 2014