Meanwhile, at the Cleveland Clinic, Frazier and his colleagues have focused on mutations in another gene, PTEN. Compared with others who have autism, people with PTEN mutations tend to process information slowly and have deficits in working memory, or the ability to hold multiple pieces of information in mind over short periods of time, the researchers reported in October9.
Those results suggest that teachers and behavioral therapists will need to adapt their methods when working with children who have PTEN-linked autism, says Frazier. They should speak slowly, for example, keep directives short and simple, and not ask the children to remember too many pieces of information at a time.
Evan Eichler, professor of genome sciences at the University of Washington.C. McLean/Univ. of Washington
People with PTEN mutations are known to have large heads, and Frazier’s team found that they have abnormally large quantities of white matter, the nerve fibers that connect brain regions. The white matter is poorly organized, which might relate to the difficulties with working memory. In contrast to the inconclusive results from brain imaging studies of people with autism stemming from a wide range of causes, the results here are striking, says Frazier. “When you look at PTEN, it’s like, ‘Bam!’ It’s huge.”
Lord agrees that puzzling out the different genetic subtypes of autism is important — but she cautions that researchers may inadvertently identify patterns in a group that don’t set it apart from other groups, or may downplay the differences within a group.
“I think there’s huge pressure on the authors to find something,” she says. For example, gut problems and sleep problems are common among children with autism, not just those who carry mutations in CHD8. “Ultimately what we want to know is: Could we identify these kids if we didn’t know their genetic abnormality?”
Besides, not all stories that come out of genetics-first studies of autism are going to be tidy and straightforward. Some autism genes may result in a range of phenotypes that might include neurodevelopmental disorders other than autism. Still other genes may not be associated with any predictable phenotype at all.
For some families involved in these studies, the story won’t have a neat outline. Waylon volunteered for the study (and even got a skin biopsy, despite his terror of needles) with altruistic motives — “so I can help other people with autism, and just further research about it.” But for him and his family, there are still more questions than answers.
So far, knowing that Waylon has a mutation in SETD2 is “just letters and numbers,” says Waylon’s father, Curtis Cude, an environmental chemist in Portland, Oregon. “I want to know: What does that mean? What are the shared characteristics? What does that gene actually affect?”
Luckily, Waylon seems to be doing well even without such deeper insights about the origins of his autism. While he struggled in elementary school — certain activities, such as writing, stressed him out so much that he would hide under his desk, and he was sometimes sent home for being disruptive — he now seems to have hit his stride. He started a club at his high school, commuted an hour and a half by train to his internship last summer and plans to attend college to study computer science.
Still, Waylon and his family hope they might benefit from the study more directly at some point, and are optimistic about individualized treatments. Waylon says he wouldn’t want to change his aptitude for math and science, which he sees as an important part of his identity. But if a treatment could flip a switch in his brain and make social interactions easier for him, he’d be all for it, he says. “It sounds like it would probably only give positive things.”