New Research May Help Explain The Genetic Roots Of Autism
SAN DIEGO, Calif. - Duke University Medical Center researchers have found evidence of a genetic link between autism and several chromosomomal anomalies. These findings, in addition to other recent Duke research discoveries on the genetics of autism, will be presented at the International Meeting for Autism Research Friday and Saturday (Nov. 9-10) in San Diego.
Another presentation by Duke researchers includes findings that show a possible link between autism and Rett's disorder, a developmental illness primarily occurring in girls that is characterized by profound mental retardation.
On Friday, they also announced a new consumer Web site dedicated to the genetics of autism.
Autism is a complex disease that affects from two to 10 per 10,000 people, making it the third most common developmental disability. However, because the disease presents varying symptoms, doctors have difficulty diagnosing it with certainty. Some autistic children simply talk later than normal, while others severely withdraw or display self-destructive patterns, such as repetitive head banging.
The evidence for a genetic basis for autism has been well established. To date, more than five possible loci, or specific regions of DNA, have been identified that could potentially lead to an increased risk of autism.
"Duke is making a major commitment to research in the genetics of autism and related disorders," said Margaret Pericak-Vance, director of the Center for Human Genetics at Duke. "Genetics will help us find the underlying cause of autism. If we find the underlying cause, it will help us target possible therapies and keys to prevention."
The research projects were led by Pericak-Vance and John R. Gilbert, Ph.D., of the division of medical genetics in Duke's department of medicine.
Duke Study Points To Chromosomomal Anomalies Suspected Of Being Involved In Autism
Duke researchers have identified seven chromosomal anomalies on six chromosomes in 12 children with autism. The findings indicate the anomalies might be associated with autism. If so, they are significant because they could help researchers identify genes involved in causing autism, said Chantelle Wolpert, a research associate with the Duke Center for Human Genetics.
"Chromosome anomalies can occur by chance and may be unrelated to autism. Our job now is to sort out which anomalies are due to chance and which ones are involved in causing autism," Wolpert said.
A chromosomal anomaly is an extra piece, or sometimes a missing piece, of a chromosome. Chromosomal anomalies have been associated with Down syndrome, in which a child inherits an extra piece of chromosome 21.
The researchers examined the frequency of chromosomal anomalies in 333 patients with autism. They identified anomalies on regions of chromosomes 2, 7, 15, 18 and X. Some anomalies were identified more than once.
They also identified, in one child, a Robertsonian translocation anomaly involving chromosomes 13 and 14. A Robertsonian translocation occurs when two chromosomes fuse together; in this case, chromosomes 13 and 14 joined together, leaving an individual with 45 chromosomes instead of 46.
One of the anomalies, an extra piece of chromosome 15, was found in five children. "The repeated occurrence of this particular anomaly suggests that it may be involved with autism, but we have more work to do to prove this.
"It has been reported before that in some children with autism, there is an extra piece of chromosome 15, but in this study, we look at a series of families, which offers more conclusive evidence.
"Previously, some scientists doubted whether chromosomal anomalies, such as those on chromosome 15, could lead to autism. But in our study we are beginning to build a case that this chromosomal abnormality could possibly cause autistic disorder," Wolpert said.
Duke Study Finds Link Between Autistic Disorders And Rett's Syndrome
Duke researchers have found genetic mutations in the MeCP2 gene of two girls diagnosed with autism. The finding is significant because MeCP2 has been implicated in Rett's disorder, a pervasive developmental disorder characterized by profound mental retardation.
The study focused on 69 females who were diagnosed with autism but did not show any clinical signs of Rett's disorder. Researchers conducted genetic tests to look for the presence of mutations in the MeCP2 gene, which they found in two of the girls. "This is significant because these were individuals who did not fit the classic phenotype of Rett. It suggests that we really need to look more carefully at our populations because this genetic mutation might be present in individuals thought to have autism," said Dr. Michael Cuccaro, associate professor of neuropsychiatry at the University of South Carolina, Columbia, and a collaborator on the project. Cuccaro has accepted a position with the Center for Human Genetics at Duke and will officially join the Duke team on Dec. 1.
In girls with Rett's disorder, very early development is normal but, as the child ages, the characteristics of Rett's disorder, such as smaller than normal head size (a condition called microcephaly) and loss of ability to control one's hands, begin to surface. Generally, Rett's disorder, which primarily strikes girls, is a progressive disease that ultimately leads to severe mental retardation by early adulthood.
The finding will help genetic researchers better understand the underlying causes of autism and Rett's disorder.
While it is known that there are many complex genetic roots to autism, Cuccaro said, the genetics of Rett's disorder, are comparatively simpler - more than 80 percent of patients diagnosed with Rett's have a specific mutation in the MeCP2 gene on the X chromosome. This mutation is not inherited, but occurs after conception.
Please visit the following URL for a news release issued in May 2001 featuring the study on MeCP2: http://www.dukemednews.duke.edu/news/article.php?id=2084.
Web Site Focuses On Advances In Genetics-Based Autism Research
The Duke Center for Human Genetics, in conjunction with Dr. Susan Folstein at Tufts University and the National Alliance for Autism Research, is preparing to launch a Web site dedicated to highlighting advances in genetics-based autism research.
The Web site www.exploringautism.org will inform parents of advances in genetics based research, said Margaret Pericak-Vance, director of Duke's Center for Human Genetics and director of the Web site.
"This Web site is dedicated to helping families who are living with the challenges of autism stay informed about the exciting breakthroughs surrounding the genetics of autism. We will explain genetic principles as they relate to autism, provide the latest research news and seek input from parents. Together we will work to increase the body of knowledge about autism.
"As research teams around the globe seek to understand the genetic contribution to autism, we are hopeful that we will develop effective treatments for autism and the disorders related to it," she said.
The Web site will feature: the story of a family in which two of three young sons have been diagnosed with autism; a genetics primer for parents; an easy-to-understand diagnostic summary of pervasive developmental disorders; and a lay language summary of the status of genetic research findings in autistic disorder. The Web site, which is funded by the National Alliance for Autism Research, will be launched Jan. 1, 2002.
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The Center for Human Genetics is one of five research centers within Duke's Institute for Genome Sciences and Policy (IGSP). The IGSP, established in 2000 with $200 million in institutional funds, also includes: the Center for Genome Technology, the Center for Human Disease Models, the Center for Bioinformatics and Computational Biology and the Center for Genome Ethics, Law and Policy.