By Charlene N. Rivera-Bonet, Waisman Science Writer
A new study led by Nell Maltman, PhD, a research scientist in the lab of Audra Sterling, PhD, associate professor of communication sciences and disorders, will investigate if language differences can predict the development of a neurodegenerative disorder in people that carry a premutation of the gene FMR1. Maltman was awarded an Early Career R21 grant from the National Institute on Deafness and Other Communication Disorders within the NIH for the study.
The FMR1 premutation affects the gene that when “fully mutated” causes fragile X syndrome (FXS), the most common inherited cause of intellectual disability. The premutation is present in one in 150 women and one in 470 men, and although carriers don’t present with FXS, the premutation alone is associated with a range of different clinical outcomes.
One possible outcome is fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative condition. FXTAS is characterized by problems with movement – such as tremors – and cognition or thinking abilities, similar to those seen in Alzheimer’s and Parkinson’s disease. Symptoms typically develop after the age of 50.
When fragile X was first discovered, premutation carriers were only thought of as having a gene that was unstable and could mutate to the full mutation form of fragile X. Over time, scientists found that individuals who are premutation carriers are at risk for a number of clinical problems. Often times, premutation carriers learn about it when they have a child who is diagnosed with fragile X.
Currently, there is no way of predicting if a premutation carrier will go on to develop FXTAS. However, other research has shown that language predicts neurocognitive decline in neurodegenerative diseases such as Alzheimer’s up to 20 years before diagnosis. “So, I was really interested in seeing if we can use language as a potential predictor of who’s going to go on to have this neurodegenerative condition, [FXTAS],” Maltman says. “If you can see slight changes earlier, maybe you can predict the outcomes later.”
Premutation carriers show age-related changes in social language skills and word production. These language differences are linked to executive dysfunction – or tasks like planning, and working memory. “And those things work together pretty well. Executive function affects language and vice versa. It’s possible that difficulties in executive functioning might be exhibited in language,” Maltman explains. Both executive function and language difficulties may also have adverse impacts on quality of life.
The study will recruit a sample of 60 premutation carriers, and 40 healthy age- and sex- matched controls between 30-65 years old. Each participant will complete language elicitation and executive function tasks, and self-report measures of quality of life. Maltman will then compare language use between carriers and matched controls, look at the role of age and executive function on language, and determine the impact of language and executive function on quality of life. Participation in this study will be fully virtual, which will allow for recruiting participants from across the U.S.
From a clinical and population health perspective, the commonness of the FMR1 premutation makes it an important target for research. “But it’s also really important to that community to better understand potential predictors of FXTAS,” Maltman says. “I have interacted with premutation carriers who are worried that they’re going to have this neurodegenerative condition. But they don’t know. Are there any signs earlier that we can identify? This is just one possible avenue.”
The NIDCD Early Career R21 support scientific research from scientists who are beginning to establish their independent research career. Maltman’s research project will be funded for three years, with a budget of $375,000.
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