NARSAD Independent Investigator Dr. Catalina Betancur has succeeded in finding powerful but uncommon "one-hit" genetic errors in a growing number of autism patients who have taken part in studies in which she is involved.
As a result, Betancur has enjoyed what for a research scientist is perhaps the rarest of satisfactions: with the help of clinical geneticists, she has shared precise knowledge of disease causation in specific cases with families of affected individuals. "We've had this opportunity several times, and it is really wonderful - this is information that can truly be life-changing for a family."
Betancur participates in two important autism projects in France, where she is an Investigator at INSERM, the French equivalent of America's National Institutes of Health. At her lab in Paris, she has access to patients enrolled in the Paris Autism Research International Study (PARIS) and participates in the multinational Autism Genome Project (AGP), a large-scale study involving thousands of autism patients, their relatives and healthy controls.
Her goal is to learn how very rare genetic variations perturb the biology of the developing brain to cause the wide range of symptoms - from severe and debilitating to comparatively mild - seen across autism spectrum disorders, or ASDs.
Betancur not only scrutinized DNA samples of people with ASDs; she also makes a point of examining carefully the clinical information about the individuals she studies. She begins from clinical signs and works her way back toward the genetic mutations that are the root cause. She's well-suited for this task, having been trained in clinical medicine and neuroscience and genetics. Betancur, whose father is a neurologist, remembers "always wanting to be a doctor, like him," but being interested also in "the question of how the brain works." After earning a M.D. in her native Colombia, she pursued a Ph.D. in neuroscience in France, and then began to study autism.
"We find many rare variations in patients with ASDs. But we don't know at the beginning if they're important - if they occur in a place in the genome where they might give rise to pathology." An extraordinary process of winnowing ensues, involving high-tech genome sequencing, clinical work-ups of patients, family interviews and neurobiology studies. "When we find a candidate genome variation, we do experiments to determine if this area contains a gene of importance in brain development."
Knowing genes and pathways involved in ASDs is the starting point for development of future therapies. It is also a basis for the genetic counseling that Betancur and colleagues have seen change lives. If a rare variant found to cause autism is de novo - if it occurred spontaneously in the fertilized egg at the time of conception - then by definition, the parents are not carriers, nor are any other relatives. If a variant is inherited, then it has precise implications for parents, siblings, even cousins. "This is information that helps everyone make reproductive decisions. And being able to help families is what makes me absolutely passionate about the work I'm pursuing with my new NARSAD grant," Betancur says.