CAR Researchers Zero in on Genetic Risk Factors for ASD


Genetics or Environment?  It’s a familiar debate that plays out as scientists search for the causes of most health conditions. Autism is no stranger to this debate, and research has shown the answer likely lies in the middle – where genetics and environment both contribute to the diagnosis of autism spectrum disorder (ASD).  ASD is considered a complex genetic disorder because even though numerous sibling studies have shown that genetics contribute to ASD, not all identical twins have ASD; researchers know that something else is involved in the development of ASD for many individuals. Early findings from a recent CAR study zero in on a specific region of DNA that may be particularly important to ASD.

In most cases, it’s difficult to identify a specific genetic change that caused person to develop ASD; however, scientists have been able to identify a clear genetic cause in a small proportion of cases. These can be chromosomal abnormalities, changes in single genes, or copy number variants (gene deletions and duplications).  As scientists continue to pinpoint which chromosomes and genes may play a role in autism, they have discovered that least 5% of individuals with ASD carry what’s known as a “copy number variation” (CNV) in their DNA. A CNV is a deletion or duplication of a small section of DNA. When a person has a duplication, they have an extra copy of that section of DNA- including all of the genes in that section; and in the case of a deletion, a person is missing a copy of a DNA section - along with the genes it would contain.

One genetic condition known as 22q11.2 Deletion/Duplication Syndrome (DS/DupS) has been closely tied to autism spectrum disorder. About a fifth of people with a 22q-related syndrome also meet gold standard criteria for an ASD diagnosis (14-25% of those with a duplication, and 18% of those with a deletion). The usual deletion or duplication of 22q11.2 involves approximately 50 genes.

In a recent study, CAR researchers sought to understand which of these genes in particular might be responsible for the increased rates of ASD. To do this, they enrolled 46 patients with “nested” deletions or duplications of the 22nd chromosome, meaning that instead of the deletion/duplication affecting all 50 genes, a smaller portion of genes were involved for these patients. For example, some people were missing approximately the first 25 genes (the LCR-A to LCR-B region), while others were missing the last 25 (LCR-B to LCR-D region) or the last 15 genes (LCR-C to LCR-D). Some of the patients had ASD and some did not. Caitlin Clements and her team discovered that among the 25 patients with a 22q11.2 deletion, all of the patients with ASD were missing a very specific region of DNA: the first 25 genes (the LCR-A to B region). In this study, when a patient’s deletion did not involve any of these first 25 genes, they did not have ASD. “This is exciting because we narrowed the ASD-risk region from approximately 50 genes to around 25,” said Clements. “If we can replicate these findings in another study, then we would suggest that future genetics research should include studies of these 25 genes to determine which ones are contributing to ASD.” This study also found that in people with a nested deletion on the A-B region, the risk of having other conditions, such as heart, hearing, mental health or gastrointestinal disorders, seemed to be similar to people who had 22q11.2 but not a nested deletion (or duplication).  

Since 22q.11.2 Deletion/Duplication Syndrome with a nested deletion on the A-B region is an extremely rare diagnosis, this study needs to be reproduced. “Families came from other states to participate, and we are very grateful because this new knowledge would not exist without them,” said Clements. Clements suggests future research should “focus on the relationship between ASD and genes in the A-B region” of 22q11.2.

For clinicians, this study confirms that patients with a nested 22q11.2 deletion or duplication should receive the same screening and recommendations as patients with a classic, larger 22q11.2 deletion or duplication. Previously, there were no screening recommendations specific to patients with nested 22q11.2Dup/DS. For families with a child diagnosed with this rare nested deletion, this study provides information on what to possibly expect for their individual child’s condition, instead of basing their expectations on information about a slightly different condition.

For readers interested in learning more, please visit the CAR Autism RoadmapTM to read about the genetics of ASD and about ASD diagnosis and other genetic conditions. If your family is interested in being a part of the largest-ever study of the genetics of autism without ever leaving home, learn more about the SPARK study here: