Study reveals a molecular connection between autism and myotonic dystrophy

A recent discovery of a molecular connection between autism and myotonic dystrophy, a type of neuromuscular disease, may provide a breakthrough on how clinicians approach autism spectrum disorder.

The new study by an interdisciplinary team of biomedical scientists, published on April 21 in Nature Neuroscience, used myotonic dystrophy as a tool or model to learn more about autism – effectively using one disorder to better understand the other.

We identified a new pathway that can lead to autism. We found that a genetic mutation in a certain gene can disrupt the expression of multiple autism-related genes during brain development, causing autism."

Łukasz Sznajder, UNLV geneticist and research lead 

Sznajder took the lead in coordinating this intercontinental scientific effort from The Hospital for Sick Children (SickKids; Toronto), University of Florida, Adam Mickiewicz University (Poland), and UNLV.

Resources were pooled between all parties, integrating dozens of autism-relevant datasets, human and mouse brain samples, cell lines, genetic constructs, and behavioral testing of mice models.

"A mutation really stood out to me that we see in rare neuromuscular diseases," said Sznajder. "This is how we started connecting the dots. We found a molecular link, or overlap, which we believe is the core of causing autistic symptoms in children with myotonic dystrophy."

The gene DMPK, which ultimately regulates muscle and brain cells, carries the mutation that causes myotonic dystrophy. These genes are eventually made into RNA and then proteins. When mutated DMPK RNAs are created, they act as a sponge and absorb otherwise healthy proteins from the muscleblind-like (MBNL) family of genes – disrupting muscle and brain development.

"MBNL proteins regulate a process called splicing, which edits other RNAs to keep the instructions, or important parts intact," said UNLV neuroscientist and co-author Rochelle Hines. "The research shows that the autism-risk genes, themselves, are not mutated in myotonic dystrophy, but affected somewhere downstream in the splicing process - resulting in the characteristic features of autism." 

Repetitive behaviors, restricted interests, and problems with social interactions are among the primary criteria for autism. Sznajder says about 95% of children with autism have an additional symptom, and that there is a comorbidity between autism and more than 100 other diseases, including myotonic dystrophy.

"Are there any other neurological diseases that could help us understand the cause of autism more?" said Sznajder. "This is but a particular piece in the puzzle of autism, and it's super exciting to see curiosity rewarded."