By Ashley Brenton, PhD
Autism Spectrum Disorder (ASD) is an excellent target for precision medicine. Genomic studies have shed light on a number of genes that are associated with ASD. Furthermore, novel precision medicine treatments, based on genetics, are currently in development.
According to the National Institute of Mental Health, Autism Spectrum Disorder (ASD) includes a cluster of developmental disorders that may present as difficulty with interpersonal relationships and social interactions, as well as repetitive behaviors. As Autism is a spectrum disorder, there is great variation in the behaviors of individuals with autism. ASD is a common disorder, with 1 in 68 children affected, according to the Centers for Disease Control (CDC)* 1 .
Multiple genes and mutation types have been identified that demonstrate causality with ASD. Several interesting studies have demonstrated that rare genetic mutations are causative in 10-30% of those with ASD *2-4 . If we include common genetic variants, this percentage increases to nearly 50% 5 . This means that there is a direct, genetic link to individual mutations in many of those with ASD. As our knowledge of genomics continues to increase, it is likely this percentage will continue to rise. In fact, in 2000, only 2-3% of those with ASD had an identified genetic link *5 . Interestingly, unlike in many conditions, no single genetic mutation has been found in everyone with ASD. Possibly this is due to the spectrum nature of ASD, as well as the interaction of genes, environment and other factors.
Many of the genes implicated in ASD are important in the central nervous system and some are also associated with other neurodevelopmental disorders, including Fragile X Syndrome and Attention Deficit Hyperactivity Disorder.
Identifying the genetic variations that are associated with ASD allows the development of exciting treatment options. One of these focuses on a gene called SHANK3. SHANK3 is critical to brain development. Around 1% of people with ASD lack a working copy of the gene. Based on this knowledge, researchers speculated that restoring the function of SHANK3 in those individuals could “rewire” the brain, eliminating ASD in that person. Thus far, only studies in mice have been conducted *6 as a first step, but the results were promising. Scientists developed
a mouse model that allowed them to turn the SHANK3 gene on or off. When they turned SHANK3 on, ASD type behavior and deficiencies disappeared. This is exciting because it suggests that a similar strategy could be used successfully in humans. Future studies in humans are required prior to its adoption as a treatment method.
SOTERIA is thrilled to be on the forefront of these advances in medicine and to help individuals understand the opportunities that exist in precision medicine. SOTERIA serves as a resource for individuals to provide expertise in the interpretation of genomic sequence data and complex scientific information.
*1. Christensen DL, Baio J, Van Naarden Braun K, et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years-- Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012. Morbidity and mortality weekly report Surveillance summaries (Washington, DC : 2002) 2016;65(3):1-23. doi: 10.15585/mmwr.ss6503a1 [published Online First: 2016/04/01]
*2. Buxbaum JD. Multiple rare variants in the etiology of autism spectrum disorders. Dialogues in clinical neuroscience 2009;11(1):35-43. [published Online First: 2009/05/13]
*3. Sanders SJ, He X, Willsey AJ, et al. Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci. Neuron 2015;87(6):1215-33. doi: 10.1016/j.neuron.2015.09.016 [published Online First: 2015/09/25]
*4. Ronemus M, Iossifov I, Levy D, et al. The role of de novo mutations in the genetics of autism spectrum disorders. Nature reviews Genetics 2014;15(2):133-41. doi: 10.1038/nrg3585 [published Online First: 2014/01/17]
*5. Vorstman JAS, Parr JR, Moreno-De- Luca D, et al. Autism genetics: opportunities and challenges for clinical translation. Nature reviews Genetics 2017;18(6):362-76. doi: 10.1038/nrg.2017.4 [published Online First: 2017/03/07]
*6. Mei Y, Monteiro P, Zhou Y, et al. Adult restoration of Shank3 expression rescues selective autistic-like phenotypes. Nature 2016;530(7591):481-4. doi: 10.1038/nature16971 [published Online First: 2016/02/18]
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Dr. Ashley Brenton is a precision medicine veteran. A classically trained molecular biologist, Dr.
Brenton’s career has focused on applying genomics to public health issues and she has a proven
track record in building scientific evidence for precision medicine, as well as bringing successful
precision medicine tests to commercialization. Dr. Brenton began her career at Johns Hopkins
and her background in public health and genomics led her to Soteria, where she strives to help
patients and their families navigate the often-complicated world of medicine through clear
communication and an expert understanding of cutting-edge medical testing.