Gene mutations in autism are more complex than thought, and while the hereditary link is a piece of the puzzle, environmental factors are increasingly so.
With incidences of autism now at alarming levels, 1 in 110 children (1 in 70 boys), the exact triggers for this complex spectrum disorder remain puzzling. Scientists do agree however, there is no single cause. Coordinated research efforts in the medical, genetic and environmental fields continue to work to pinpoint the mechanisms that “turn on” autism.
Most recently in autism research news, findings across three studies indicate that changes in DNA may produce what are essentially different forms of autism.
Gene Mutations Complex in Autism Spectrum Disorders: Multiple Forms of Autism
Most scientists believe autism is caused by various abnormalities in the brain structure or function, the result of hundreds of mutations, many which occur spontaneously. Identifying the sequence of events that causes autism whether the result of genetic or environmental factors or a combination of both requires the continued worldwide collaboration among scientists, clinicians, advocacy groups and families, some of whom have a bias towards the hereditary explanation or the environmental.
Recent findings indicating that gene mutations found in people with autism are very complex and may account for various forms of autism don’t address to what degree genetic or environmental factors trigger symptoms. The findings can, however, help scientists better pinpoint which genes may be involved in the mutations that occur from various triggers.
Gene mutations can result from copy-number variations (CNVs) across a number of specific genes. CNV means that a relatively large number of a person’s genome (all the genetic material for an organism e.g. brain cells, organs, etc.) has been deleted or duplicated, causing abnormalities in the chromosomal sequence. The addition or deletion of a gene can drastically change gene expression and account for abnormalities in development, behavior and disease resistance.
The two teams involved in the recent study identified a few dozens of these spontaneous mutations, although there may, however, be as many as 300, explained Michael Ronemus, co-author for one of the team’s involvements in the study. As this analysis continues, the results may help identify a number of distinct subtypes of autism, says Ronemus.
While these findings don’t give families with autism immediate benefit, they will help researchers better understand the genetic causes and target treatments. For instance, research on synapse formation and function could produce treatments to address the flow of signals between nerve cells.
“For the first time we’re getting a sense of how many areas of the genome are likely to contribute to autism,” said Dr. Matthew W. State, associate professor of psychiatry and of genetics at Yale University quoted in the article, and the lead investigator of one of the reports. “We know there are multiple, different ways to get autism.“
Targeting Hereditary Pathways in Autism Families, Key Chromosomes and Gender Differences
The heritability of autism is not entirely clear although some estimates write the Los Angeles Times, suggest 25% of autism cases are inherited gene mutations passed from parent to child. Yet while some of the high-risk genes have been identified, researchers are mystified by what causes the disorder in families with no history of autism.
Both research teams involved with analyzing the DNA data across 1,000 families identified chromosome No. 7, a key chromosome in the development of social personality. Researchers already knew that if that region, referred to as 7q11.23, is deleted it causes Williams-Beuren syndrome, a rare neurological disorder characterized by a highly social personality. The new findings indicate duplications in the same region are linked to autism spectrum disorder.
As researchers continue to pinpoint which genes duplicate or delete to trigger autism, they’ll also work to determine what causes the spontaneous mutations in the first place. Mutations sometimes surface in the parents’ germ lines, which give rise to sperm and eggs, and either father or mother can be the source.
The recent findings also revealed intriguing differences between boys and girls: “Mutations occur at the same rate in males and females, but in females, the mutations will not have such a devastating impact,” Ronemus said, “We don’t understand the basis for that.“
While reported rates of autism have increased in recent decades, some scientists believe this is due to greater awareness of the condition and therefore increased diagnosis. Others in the field, however, believe environmental factors can no longer be ignored.
Environmental Factors Included in the New Paradigm of Autism
The Autism Society of America (ASA) writes on their website, “Research indicates that other factors besides genetic components are contributing to the rise in increasing occurrences of ASD, such as environmental toxins (e.g., heavy metals such as mercury), which are more prevalent in our current environment than in the past. Those with ASD (or those who are at risk) may be especially vulnerable, as their ability to metabolize and detoxify these exposures can be compromised.“
According to the ASA, findings indicate that children with autism or who are at risk have a metabolic impairment that reduces their ability to rid their bodies of heavy metals and other toxins. The build-up of these toxins in the body can lead to brain and nervous system damage and developmental delays.
Michael Lerner, Ph.D writes in his article, “Autism’s New Paradigm: Seeking Answers to Environmental Threats” (Autism Advocate, 2006), “The new paradigm of autism proposes the following: autism is not a strictly inherited disease; environmental factors contribute to its incidence, and dietary interventions; detoxification strategies and other treatments may contribute to amelioration or even recovery.”
Lerner explains that what exists is a complex interaction among genetic inheritance, gene expression as modified by fetal exposure to endocrine-disrupting chemicals (the concern among some families due to mercury used in preservatives in select vaccines) diet, stress, income disparities, ethnicity, exercise, and numerous other factors. As a result, says Lerner, searching for a single cause is pointless.
Lerner argues that under the current health sciences revolution, both environmental and inherited factors must inform the clinical, research and policy issues. There are committed scientists on either side, however, those who feel strongly that environmental factors play no role in autism, and those who are equally certain they do. In the middle says Lerner, is a “wide spectrum of people who are open to the new paradigm of autism hypothesis but are not certain whether it is true or what to what extent it is true.“
Planet Instability Producing Toxin Build up, Contributing to Disease Increase
In the same issue of Autism Advocate Martha R. Herbert, M.D., Ph.D. argues that we now know enough to take the relationship between environmental factors and autism seriously. Under this new paradigm of working with environmental triggers, we are implored to work on autism prevention relative to what can be controlled, at least for some forms of autism. Herbert continues to argue her point by asking the autism community to consider the following:
“If we assume that autism is mainly or purely genetic and not environmental, we are implying that nothing has changed in the environment that would alter genes or the ways that genes are expressed. Can we really defend the claim that the environment is stable? Hardly. Consider the following unprecedented problems:“
- The rise in invention and use of chemicals that are noxious and toxic by design and also have unintended consequences. These include pesticides and industrial solvents.
- The increase in human diseases such as cancers, chronic, allergic, immune, autoimmune and degenerative diseases.
- The rise in infectious and cancerous illnesses and malformations in animals.
- The loss of biodiversity with the highest rate of extinction of planet and animals species since the
- Age of the Dinosaurs, including the loss of cultural diversity that spreads ecologically adaptive health-promoting traditions.
- The growing number of dead zones in coastal oceans near large population settlements, with enormous ocean pollution and the dying out of fish stocks.
- The evidence that global climate change seems to be advancing faster than anticipated.
Herbert proposes based on a bottom line summary from the Millennium Ecosystem Assessment that there is “no way to defend the claim that our environment is stable” and so she asks, “Why would human children, and their developing brain and bodily systems, be spared?“
While the precise combination of genetic and/or environmental triggers for autism spectrum disorders remains a puzzle, recent findings illuminate that a number of gene mutations may be responsible for different forms of autism. And, despite continuing disagreement among the autism community about the primary triggers, an increasing number of people believe environmental factors should be considered as a possible contributor to the rise of autism.
It is this expanding paradigm combined with the on-going international and multi-disciplinary research collaboration that will likely yield the most promising hope for prediction, treatment, and a cure. And, in the wake of such comprehensive efforts to find a cure, researchers’ understanding of other diseases that are triggered by a complex interplay of genetic and environmental factors such as Parkinson’s, Alzheimer’s, Lupus, will advance.
Disclaimer: The information contained in this article is for educational purposes only and should not be used for diagnosis or to guide treatment without the opinion of a health professional. Any reader who is concerned about his or her health should contact a doctor for advice.
- “Autism Causes.” Autism Society of America. Retrieved October 24, 2018.
- Roan, Shari, (2011, June 9) “Autism linked to hundreds of genetic mutations.” articles.latimes.com. Retrieved October 24, 2018.
- Schaaf, Christian P., Zoghbi, Huda Y. “Solving the Autism Puzzle a Few Pieces at a Time.” Neuron. June 9, 2011 (Vol. 70, Issue 5, pp. 806-808).
- Lerner, Michael Ph.D., “Autism’s New Paradigm: Seeking Answers to Environmental Threats.” Autism Advocate (Fifth Edition, Volume 45, No. 5).
- Herbert, Martha, M.D., Ph.D. “Time to Get a Grip: Does an environmental role in autism make sense? How do we decide?” Autism Advocate (Fifth Edition, Volume 45, No. 5).