Exome Sequencing in Autistic Spectrum Disorder

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Overall Status

Completed

CT.gov ID

NCT01059201

Collaborator

(none)

322

Enrollment

Locations

87.8

Duration (Months)

107.3

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder Autism Autistic Disorder

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.

Study Design

Study Type:

Observational

Actual Enrollment :

322 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

Exome Sequencing in Autistic Spectrum Disorder Patients With Altered Cholesterol Homeostasis

Study Start Date :

Jan 21, 2010

Study Completion Date :

May 15, 2017

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

INCLUSION CRITERIA:

Prior participation in Autism Genetic Research Exchange
Multiple affected children with ASD
Willingness to contact the NIH and reconsent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kennedy Krieger Institute	Baltimore	Maryland	United States	21205
2	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892
3	Ohio State University	Columbus	Ohio	United States	43210-1240