The frequency and severity of symptoms associated with fragile X spectrum disorders in the rural town of Ricaurte in Colombia are much higher compared to those of the general population, a study has found. Researchers believe such differences may be because of higher exposure to toxic pesticides.
Fragile X syndrome (FXS) is the most frequent single genetic cause of autism spectrum disorder (ASD). FXS is caused by the expansion of CGG repeats in the fragile X mental retardation 1 (FMR1) gene, which provides instructions for making a protein called fragile X mental retardation protein (FMRP).
Unlike individuals carrying the full mutation (those who have more than 200 CGG repeats), premutation carriers (those who have 55 to 200 CGG repeats) usually maintain their intellectual abilities.
Even so, it is estimated that 20% of premutation carriers are affected by developmental problems or ASD, which are included in the fragile X spectrum disorders (FXSD), and nearly 50% have psychiatric disorders, such as anxiety, attention deficit hyperactivity disorder (ADHD) and depression.
FXSD also includes other types of disorders, including fragile X-associated primary ovarian insufficiency (FXPOI), a condition that compromises women’s ovary function, and fragile X-associated tremor/ataxia syndrome (FXTAS), a condition that mostly affects older patients and is characterized by motor and cognitive impairments.
Previous studies in animal models have suggested that neurons from FMR1 premutation carriers are more vulnerable to environmental toxins.
Interestingly, the incidence of FMR1 mutations in Ricaurte, which relies mostly on “agriculture and cattle raising, which are practiced without the aid of industrial equipment and often under precarious working conditions,” is much higher compared to that of the general population.
To assess the frequency and severity of FXSD, including clinical signs of FXTAS, FXPOI, seizures, and behavioral and cognitive deficits, researchers analyzed 25 premutation carriers (20 women and five men) from Ricaurte.
Among those older than 50, 50% of men and 33.33% of women showed signs indicative of FXTAS. In addition, 18.7% of women carrying the FMR1 premutation had FXPOI, while 25% showed signs suggestive of ovarian insufficiency.
Five female premutation carriers (25%) were affected by seizures, while cognitive and behavioral problems were observed in two female and one male carrier.
“[T]he inhabitants are exposed to pesticides through their work in the fields, the common practice of storing pesticides inside their homes and/or contact with contaminated water or food. An association of these neurotoxic environmental contaminants with the exacerbation of neurological deterioration in FMR1 premutation carriers has yet to be described,” researchers stated.
“[H]owever, if true, then exposure to neurotoxic pesticides could explain the increased frequency and severity of clinical symptoms of FXTAS, FXPOI and seizures in carriers of the FMR1 premutation in this rural population,” they said.
According to researchers, identifying the specific environmental factors that interact with the FMR1 premutation is necessary because it would enable the development of interventions that may lessen the incidence and severity of clinical symptoms.
“This information may also provide useful insight in identifying genetic subgroups in the population that are more vulnerable to pollution. This should hopefully lead to better laws to protect the general population from this type of pollution,” they concluded.