Experts estimate that nearly 1 in 88 children are affected by autism spectrum disorders. Symptoms can range from mild personality traits to severe intellectual disability and seizures.
Heredity plays a large role in autism, and professionals say an understanding of the altered genetic pathways is critical for diagnosis and treatment. Unfortunately, the complexities of the genetic variances responsible for disorders have challenged researchers.
“Autism is the most inheritable of neurodevelopmental disorders,” said Rajini Rao, Ph.D., of Johns Hopkins University in Baltimore, Md., “but identifying the underlying genes is difficult since no single gene contributes more than a tiny fraction of autism cases.”
Rather, she said, “mutations in many different genes variably affect a few common pathways.”
In a new study, a team of scientists at Johns Hopkins and Tel Aviv University in Israel looked at genetic variations in DNA sequence in the ion transporter NHE9. They found that autism-associated variants in NHE9 result in a profound loss of transporter function.
“Altering levels of this transporter at the synapse may modulate critical proteins on the cell surface that bring in nutrients or neurotransmitters such as glutamate,” said Rao. “Elevated glutamate levels are known to trigger seizures, possibly explaining why autistic patients with mutations in these ion transporters also have seizures.”
The research was novel as the team exploited decades of basic research done in bacteria and yeast to study this complex human neurological disorder.
First, the group at Tel Aviv University, led by Dr. Nir Ben-Tal, built structural models of NHE9 using a bacterial relative as a template, allowing the Rao laboratory at Johns Hopkins to use the simple baker’s yeast for screening the mutations.
Experts say as genomic information becomes readily available for everyone, researchers will use easy, inexpensive, and rapid screening methods to evaluate rare genetic variants in autism and other disorders.
Rao and her team are optimistic about the potential benefits of their latest findings.
“Although the research is still at an early stage, drugs that target the cellular pathways regulated by NHE9 could compensate for its loss of function and lead to potential therapy in the future,” Rao said. “These findings add a new candidate for genetic screening of at-risk patients that may lead to better diagnosis or treatment of autism.”
Source: American Institute of Physics