Asperger's Study U of Pen


In this blog post, I’d like to share information on a current study at the Perelman School of Medicine at the University of Pennsylvania called the Autism Spectrum Program of Excellence (ASPE). In 2017, ASPE was established to significantly improve the understanding of the genetic causes of Autism Spectrum Disorder (ASD) in order to energize the research and clinical community across the globe.

What is Autism Spectrum Disorder?

Autism Spectrum Disorder (ASD) is the term for a broad range of developmental disorders characterized by difficulties with social skills, repetitive behaviors, speech, and nonverbal communication (eye contact, facial expressions, gestures, and body language). According to NIH, behavioral signs of ASD, such as reduced eye contact and social interaction, can sometimes be detected before age 2. However, the condition is usually diagnosed between ages 2 and 4, when more advanced communication and social skills, such as learning to play with others, typically begin to develop. In addition to those defining features, many individuals with ASD also have accompanying symptoms in the domains of attention, executive functioning, anxiety, and sleep / circadian rhythms.

The diagnosis of ASD actually includes several different diagnoses that were formerly classified as separate conditions. For example, the term “autistic disorder” was used when affected individuals had limited or absent verbal communication, often in combination with intellectual disability. By contrast, Asperger syndrome was a diagnosis previously applied to affected individuals of average or above-average intelligence who were not delayed in their language development. The broader diagnosis of ASD was created because many affected individuals fall outside of the strict definitions of the narrower diagnoses, and their intellectual and communication abilities may change over time.

What causes ASD?

There is no known single cause for ASD, but it is generally accepted that it is caused by abnormalities in brain structure or function. Specifically, autism affects information processing in the brain by altering connections and organization of nerve cells and their synapses (where nerve cells come together and communicate with each other). How this occurs is not well understood.

These brain abnormalities have been associated with a combination of genetic and environmental factors. Risk factors during pregnancy include certain infections (i.e. rubella), toxins (i.e. alcohol, cocaine, pesticides, etc.), fetal growth restriction, and autoimmune diseases. You may have heard the claims that there is a link between the MMR vaccine and autism, however, these claims have been extensively investigated and found to be false. Overall, non-genetic factors may contribute up to about 40 percent of ASD risk.

The role of genetics in ASD

A gene, which is made up of DNA, is the basic physical and functional unit of heredity. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. Certain genes act as instructions to make proteins. However, not all genes code for proteins. Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. This is called genetic variation. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.

Problems can arise when genes mutate. This is because cells can only function correctly if proteins do their jobs in the right places at the right times. Sometimes, gene mutations prevent one or more of these proteins from working properly. If a gene’s instructions for making a protein are altered, a mutation can cause the protein to malfunction or to be missing entirely. When a mutation alters a protein that plays a critical role in the body, it can disrupt normal development or cause a medical condition.

According to NIH, changes in over 1,000 genes have been reported to be associated with ASD, but a large number of these associations have not been confirmed. Many of the genes associated with ASD are involved in the development of the brain. The proteins produced from these genes affect multiple aspects of brain development, including production, growth, and organization of neurons. Some of the genes that have been associated with ASD include ARID1B, ASH1L, CHD2, CHD8, DYRK1A, POGZ, SHANK3, SYNGAP1, and NRXN1.

ASPE genomics studies

The University of Pennsylvania ASPE study is unique because the researchers are focused on the genomics of Asperger syndrome, which, as mentioned above, is part of the umbrella diagnosis of ASD. There have been other studies focusing on the genomics of ASD, usually more symptomatic forms of ASD, but the ASPE researchers theorize that they can learn new things about the genomics of ASD as a whole by focusing on Asperger syndrome. Studying traits related to Asperger syndrome as traits that occur and vary across a spectrum provides a window into the biology behind this condition. By better understanding the biology, researchers can develop better ways to diagnose and treat ASD.

A major focus of ASPE genetic studies will be on the NRXN1 gene, which codes for the protein neurexin 1. Neurexins are a family of proteins that function in the vertebrate nervous system as cell adhesion molecules and receptors. Mutations of the NRXN1 gene have been associated with autism, schizophrenia, and other psychiatric and neurodevelopmental disorders.

One of the things that makes the ASPE study really powerful is the use of a family-based genomics approach. In many genomics studies, individuals with ASD and perhaps their parents and siblings are studied. However, in the ASPE family-based genomics approach, the researchers are going to study individuals on the spectrum and all members of extended families, including their parents, siblings, grandparents, uncles, aunts, and cousins. A family-based genomics approach enables the researchers to study the effects of rare genetic variance and traits related to Asperger syndrome.

Furthermore, unlike most previous autism genetics studies, the ASPE Program is focusing the recruitment efforts of their genomics study on individuals with ASD without intellectual disability, which will lead to new insights into the genomics and biology of the entire autism spectrum. Ultimately, these insights will help the ASPE researchers to develop improved diagnosis and treatments, and improve the quality of life of individuals on the spectrum and their families.

Join the ASPE Study

The ASPE study is recruiting adults and children age three and over with a diagnosis (or suspected diagnosis) of autism spectrum disorder (ASD) without intellectual disability. This may include individuals with Asperger syndrome, pervasive developmental disorder (PDD-NOS),  and social communication disorder. Since the study utilizes a family-based genetic approach, ASPE would also like to recruit any first-degree family members (parents, siblings, children) and second- and third-degree relatives (grandparents, grandchildren, aunts, uncles, nephews, nieces, half-siblings, first cousins) who are willing to participate in the study.

Participation will involve completing a series of online questionnaires, providing a blood sample, and wearing a small watch-like device for several weeks. For more information, leave a message for the study team by clicking here. You can also email or call 267-542-1717.


Autism Speaks, “What is Autism?”

Wikipedia, “Autism”

NIH Genetics Home Reference, “What is a Gene?”

NIH Genetics Home Reference, “How can gene mutations affect health and development?”

NIH Genetics Home Reference, “Autism Spectrum Disorder”