Exome Sequencing in Autistic Spectrum Disorder
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Psychiatric, Autism |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 4/6/2019 |
| Start Date: | January 21, 2010 |
| End Date: | May 15, 2017 |
Exome Sequencing in Autistic Spectrum Disorder Patients With Altered Cholesterol Homeostasis
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.
- 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.
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.
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.
- INCLUSION CRITERIA:
1. Prior participation in Autism Genetic Research Exchange
2. Multiple affected children with ASD
3. Willingness to contact the NIH and reconsent
We found this trial at
3
sites
Ohio State University The Ohio State University’s main Columbus campus is one of America’s largest...
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Kennedy Krieger Institute While not officially part of Johns Hopkins Medicine, Kennedy Krieger Institute is...
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9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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