Dec. 3, 1999 CHAPEL HILL - Researchers at the University of North Carolina at Chapel Hill and collaborating institutions are reporting evidence for a possible gene on chromosome 13 that causes autism. The group's report will be published December 15 in the American Journal of Medical Genetics.
Autism is considered a severe neuro-developmental disorder defined by social and communication deficits and ritualistic-repetitive behaviors that are detectable in early childhood and continue throughout life.
"For a long time autism was not viewed as being a genetic disorder," says Dr. Joseph Piven, formerly of Iowa University, now UNC-CH professor of psychiatry and new director of the university's Mental Retardation and Developmental Disabilities Research Center. "It has a high degree of heritability, confirmed by twin studies that show a substantially higher rate in identical twins - so much so that heritability is over 90%."
According to the child psychiatrist, families with an autistic child run up to a 5% risk of having a second child with autism. "And while that percentage is not so high, it's substantially higher than the rate of autism in the general population, which is approximately five in 10,000 kids. The data is pretty overwhelming that autism is strongly genetic, more so than schizophrenia or diabetes."
Still, despite epidemiology evidence of a strong genetic influence, Piven and his collaborators note that the search for autism genes has only recently begun in earnest. The new study is one of a handful worldwide to genetically screen the DNA of nuclear families of autistic siblings. This investigation involved 75 families with at least two autistic children, including three families having three autistic children. Children's ages ranged from 3 to 31 years old.
Findings were based on an assessment of participants' DNA prepared from blood samples. The researchers spaced 416 nucleotide markers on selected chromosome regions for each individual. The markers helped identify those regions across individuals containing similar clusters of nucleotide sequences. Statistical analysis then determined if the presence of these regions was significantly greater than chance. For a region of chromosome 13, the answer was yes.
The study also highlighted several other possible DNA hot spots for autism genes, notably a region on chromosome 7. This latter finding confirms a report last year by an international autism research team.
The new evidence also converges with that from another research group for a location in the same region of chromosome 7 that is currently implicated in some form of specific speech and language impairment, a disorder having characteristics that overlap that of autism.
"We believe there must be more than one gene involved in autism," Piven says. "As in all complex behavioral disorders, there's no clear evidence when looking at family pedigrees or family trees that suggests a single-gene may underlie this disorder."
In the second stage of the project, also funded by the National Institutes of Health, the research group will add 100 new families for a follow-up analysis. "By comparing results across a number of studies, we expect to be able to narrow our search for autism susceptibility genes to a small number of genomic regions," they state.
Participating institutions include New England Medical Center/Tufts University School of Medicine, Vanderbilt University School of Medicine, University of Iowa College of Medicine, The Johns Hopkins University School of Medicine, and Harvard University School of Public Health.
In addition to the genetics of autism, Piven also uses neuroimaging (with MRI) to study structural differences in the brain of autistic individuals. He was the first to report that brain size is greater in autistic persons, an enlargement that may be due to certain timing during the process of neuronal development.
With new funding from the National Institute of Mental Health, Piven's Center is conducting a longitudinal study of children aged 18-to-35 months with autism or probable autism.
"Basically, we want to look at the size and shape of the brain to gain insights into this observation of enlargement, that it may encompass some developmental abnormalities in the brain during early postnatal development," he says. Piven's neuroimaging project will enroll 35-40 children and follow them into early childhood.
Beyond autism, Piven says the Center will provide a resource to facilitate the study of mental retardation and other developmental disorders including fragile X syndrome.
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