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Missed Connections: Uncovering a Genetic Cause for Abnormal Synapses in Autism

Paige Collins

Paige Collins | Tuesday, November 8, 2016

Dr. Karun Singh's lab has identified a genetic cause for abnormal synapse development and function in autism spectrum disorders.


Autism Spectrum Disorder (ASD) is complex to say the least. As the name implies, cases of autism exist on a spectrum, with the disorder manifesting differently from patient to patient. Despite this diversity, one of the commonalities among people with ASD is that their brain connections, or synapses, aren’t forming or functioning normally.

A new study led by Dr. Karun Singh, published today in Cell Reports, sheds new light on the role of the DIXDC1 gene in regulating the formation of brain connections. In collaboration with Dr. Stephen Scherer at SickKids, Dr. Singh discovered that mutations in DIXDC1 in individuals with ASD impaired normal synaptic development.

“One of the underlying commonalities among children with ASD is that their brain connections are functioning abnormally, which is likely causing their symptoms. In our study, we have found genetic ‘glitches’ in this gene that cause that problem,” said Dr. Singh.

Dr. Singh noted that DIXDC1 is one of several genes found to disrupt the development of synapses in individuals with ASD, and pointed to drug discovery as the next logical step for these findings. Ultimately, he hopes to discover a drug that can help to improve brain function and restore plasticity by fixing the abnormal brain connections that are causing disease symptoms.

The individualized nature of cases of ASD makes developing personalized medicine especially important and Dr. Singh believes that there is no research facility better suited to tackle this challenge than the SCC-RI.

“Our commitment to working with human cells and our established drug discovery capabilities make this the best place for moving forward to patient-specific drug discovery,” Dr. Singh asserted.

Dr. Singh is excited to see the SCC-RI moving in this direction: harnessing successes in blood and cancer research, and making a lateral move towards neural disorders.

“I’m excited about what this paper means for the SCC-RI’s growing neural program; it is just starting to emerge as one of our strengths. This paper reinforces that we are serious about studying brain disorders and able to deliver.”

This research was funded by: Canadian Institutes of Health Research (CIHR), David Braley, Natural Sciences and Engineering Research Council (NSERC), Bickell Medical Foundation, Scottish Rite Charitable Foundation, Krembil Foundation, Brain Canada Platform Support Grant, Ontario Brain Institute (OBI).

Karun Singh

Karun Singh

Principal Investigator