Drs. Katy Phelan and Catalina Betancur have published a clinical utility gene card for 22q13 deletion syndrome. The card details aspects of the syndrome such as disease characteristics, test characteristics and clinical utility. To view the card, click http://www.ncbi.nlm.nih.gov/pubmed/21150887.
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A number of Shank3 mouse models have been created in an effort to explain the role that Shank3 mutations play in the development of autism spectrum disorder (ASD) features. Following the characterization of the first Shank3 mouse by Dr. Ozlem Bozdagi Gunal and her team at Mount Sinai (See previous post: New mouse model for Phelan-McDermid Syndrome), three more groups have described results with mice that examine Shank3 function.
Peça et al generated two different mouse models, referred to as Shank3a and Shank3b. They targeted different areas of the gene sequence and showed that mice lacking both Shank3a and Shank3b copies develop autistic-like behaviors, such as social interaction deficits, increased anxiety and excessive grooming.
Wang et al used a strategy similar to the one followed by Dr. Bozdagi Gunal and her team in order to create mice missing full length Shank3 (Shank3a). Dr. Wang’s team found that a loss of both copies results in social and cognitive deficits, repetitive behaviors and impairments in synaptic plasticity. Behavioral tests showed that complete loss of Shank3a led to impairments in social approach and affiliation, communication deficits, learning difficulties, obsessive behaviors and mild motor abnormalities. The team also explored the functional consequences of Shank3 loss and found that nerve cell communication in the hippocampus, a brain structure that plays an important role in learning and memory functions, was impaired.
Using a different approach Bangash et al, created a different Shank3 mouse, which results in the deletion of a section of the Shank3 protein, referred to as Shank3+/ΔC. A decrease in Shank3 levels resulted in a phenotype that included deficits in social approach and communication but left cognitive processes such as learning and memory relatively intact.
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In May Dr. Joseph Buxbaum, Director of the Seaver Autism Center, was a member of the Shank3 gene research panel at the annual International Meeting for Autism Research (IMFAR). Dr. Buxbaum and his team were the first group to publish a genetic mouse model of Shank3. This model lacks one copy of the Shank3 gene, as is the case in humans with a Shank3 mutation. Characterization of this mouse model provides clear support that Shank3 plays an important role in synapse architecture, function, and plasticity. In Dr. Buxbaum’s presentation, he also explained that his lab was able to reverse the Shank3 mutation phenotype in brain slices by administering IGF-1. The ability to reverse this phenotype is one exciting step closer to the identification of novel therapeutic targets for 22q13 deletion syndrome/Phelan-McDermid Syndrome.
To read more about this Scientific Panel, please see the blog post by Autism Speaks: http://blog.autismspeaks.org/2011/05/24/shan/.
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Dr. Joseph Buxbaum, Director of the Seaver Autism Center, has been awarded the 2011 Mount Sinai Dean’s Award for Excellence in Translational Science, for his innovative work in gene discovery and the development of novel therapeutics for neurodevelopmental disorders. Congratulations!
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On March 3-4, 2011, the Seaver Autism Center co-organized the First International Phelan-McDermid Syndrome Symposium. The Symposium brought researchers, clinicians, and parent advocacy groups together to discuss 22q13 deletion syndrome, Shank3, and the development and implementation of novel therapeutics. Dr. Joseph Buxbaum moderated a round table discussion, and Dr. Ozlem Bozdagi Gunal gave a presentation about Shank3-deficient mice.
Throughout both days of the Symposium both the theme of sharing among scientists, as well as of collaboration between researchers and families, arose frequently. The Symposium ended with breakout sessions that encouraged honest brainstorming from all involved. These ideas will serve as a valuable springboard for Shank3/PMS research and advocacy in the future.
To read more about the Symposium, please visit the PMS Foundation website. (www.pmsf.org)
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A study headed by Jacques Michaud from the University of Montreal identified a de novo splice site mutation in the SHANK3 gene in a boy with mild intellectual disability. This mutation changes the assembly of the protein during its synthesis and leads to a truncation of the longest forms of SHANK3. This truncation occurs at the beginning of the molecule in a domain called the ankyrin repeat domain. The mutation specifically disrupts the longest forms of SHANK3 and shows that loss of even these longer forms are sufficient to produce neurodevelopmental disability. Interestingly, the mouse model published by Bozdagi et al in 2010 has a very similar (though not identical) mutation. The study from the Michaud group was published in the American Journal of Human Genetics.
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Dr. Buxbaum and the Seaver Autism Center are proud to join the Singer family, and Team Drive4Rebecca in the New York City Triathlon on August 7, 2011. The Drive4Rebecca is a proud supporter of the groundbreaking research underway at the Seaver Autism Center at the Mount Sinai School of Medicine. As part of this team, we will be raising money to contribute to the Team’s goal of $100,000. Half of all the money raised by the Center will be donated to the Seaver Autism Center to support active research, while the other half will go to supporting the Drive4Rebecca’s continuing projects.
For more information and to donate, visit http://www.crowdrise.com/TeamDriveForRebecca/fundraiser/seaverautismcenter.
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The Seaver Autism Center Advances in Autism Conference will be held on Sunday, April 3, 2011. Chaired by Dr. Joseph Buxbaum, Director of the Seaver Autism Center, the conference is designed for healthcare professionals, educators, social workers and family members, and will feature Dr. Stephen Shore, EdD, who will give the Keynote Presentation, “Life on and Slightly to the Right of the Autism Spectrum: An Inside View Towards Matching Best Practice to Needs.” Dr. Shore will share his autobiographical story, and he will also demonstrate what it feels like to have autism.
For more information, please contact Jessica Brownfeld at [email protected].
To register, please go to www.mssm.edu/cme/courses/autism or contact Jeanette Cotto at [email protected].
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A new study with a woman with Phelan-McDermid Syndrome (PMS) identifies the smallest published SHANK3 deletion to date. The fact that this small deletion results in the full manifestations of PMS reinforces the finding that disruption of the SHANK3 gene results in the full range of Phelan-McDermid Syndrome phenotypes.
For the full paper, visit http://www.ncbi.nlm.nih.gov/pubmed/21271662.
Science Magazine featured the new mouse model that has a loss of one copy of the SHANK3 gene. This model was created by Dr. Joseph Buxbaum and studies by him and other investigators at the Seaver Autism Center at the Mount Sinai School of Medicine, as well as by Dr. Jacqueline Crawley at the National Institute of Health.
To read more, click below.
