Prevalence and predictors of subjective memory complaints in adult male carriers of the <i>FMR1</i> premutation

Birch, Rachael C; Hocking, Darren R.; Trollor, Julian N.

doi:10.1080/13854046.2016.1145905

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…On the other hand, linear regression models showed no correlations between clinical and molecular measures including CGG repeat numbers, FMR1 mRNA, FMRP, activation ratio, and FREE2 methylation in premutation carriers compared to the control group. These findings are consistent with previous studies [8] , [12] , [18] , [20] , [21] , [24] , [29] , [38] .…”

Section: Discussionsupporting

confidence: 94%

Clinical and molecular correlates in fragile X premutation females

et al. 2017

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The prevalence of the fragile X premutation (55–200 CGG repeats) among the general population is relatively high, but there remains a lack of clear understanding of the links between molecular biomarkers and clinical outcomes.In this study we investigated the correlations between molecular measures (CGG repeat size, FMR1 mRNA, FMRP expression levels, and methylation status at the promoter region and in FREE2 site) and clinical phenotypes (anxiety, obsessive compulsive symptoms, depression and executive function deficits) in 36 adult premutation female carriers and compared to 24 normal control subjects.Premutation carriers reported higher levels of obsessive compulsive symptoms, depression, and anxiety, but demonstrated no significant deficits in global cognitive functions or executive function compared to the control group. Increased age in carriers was significantly associated with increased anxiety levels.As expected, FMR1 mRNA expression was significantly correlated with CGG repeat number. However, no significant correlations were observed between molecular (including epigenetic) measures and clinical phenotypes in this sample. Our study, albeit limited by the sample size, establishes the complexity of the mechanisms that link the FMR1 locus to the clinical phenotypes commonly observed in female carriers suggesting that other factors, including environment or additional genetic changes, may have an impact on the clinical phenotypes. However, it continues to emphasize the need for assessment and treatment of psychiatric problems in female premutation carriers.

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Section: Discussionsupporting

confidence: 94%

Clinical and molecular correlates in fragile X premutation females

et al. 2017

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“…The use of the BRIEF-A among females with the PM has been limited to only a handful of prior studies (23,117), but is useful in that clinical significance may be easily determined and a standardized self-report measure can enable cross-cohort comparisons. Of note, however, such self-report measures could lead to over-reporting of symptoms (118,119), and so may best be interpreted within the context of results from studies employing direct assessment of executive skills.…”

Section: Discussionmentioning

confidence: 99%

The Phenotypic Profile Associated With the FMR1 Premutation in Women: An Investigation of Clinical-Behavioral, Social-Cognitive, and Executive Abilities

et al. 2021

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The FMR1 gene in its premutation (PM) state has been linked to a range of clinical and subclinical phenotypes among FMR1 PM carriers, including some subclinical traits associated with autism spectrum disorder (ASD). This study attempted to further characterize the phenotypic profile associated with the FMR1 PM by studying a battery of assessments examining clinical-behavioral traits, social-cognitive, and executive abilities in women carrying the FMR1 PM, and associations with FMR1-related variability. Participants included 152 female FMR1 PM carriers and 75 female controls who were similar in age and IQ, and screened for neuromotor impairments or signs of fragile X-associated tremor/ataxia syndrome. The phenotypic battery included assessments of ASD-related personality and language (i.e., pragmatic) traits, symptoms of anxiety and depression, four different social-cognitive tasks that tapped the ability to read internal states and emotions based on different cues (e.g., facial expressions, biological motion, and complex social scenes), and a measure of executive function. Results revealed a complex phenotypic profile among the PM carrier group, where subtle differences were observed in pragmatic language, executive function, and social-cognitive tasks that involved evaluating basic emotions and trustworthiness. The PM carrier group also showed elevated rates of ASD-related personality traits. In contrast, PM carriers performed similarly to controls on social-cognitive tasks that involved reliance on faces and biological motion. The PM group did not differ from controls on self-reported depression or anxiety symptoms. Using latent profile analysis, we observed three distinct subgroups of PM carriers who varied considerably in their performance across tasks. Among PM carriers, CGG repeat length was a significant predictor of pragmatic language violations. Results suggest a nuanced phenotypic profile characterized by subtle differences in select clinical-behavioral, social-cognitive, and executive abilities associated with the FMR1 PM in women.

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“…An expansion of more than 200 cytosine-guanine-guanine (CGG) trinucleotide repeats in the 5' untranslated region of the FMR1 mRNA causes the gene to be fully methylated, interferes with protein production, and results in the full mutation of fragile X syndrome (FXS). Prior research exploring genotype-phenotype associations has largely focused on variation at the upper end of the CGG repeat range (2)(3)(4)(5)(6). Only a small body of literature has investigated the importance of CGG repeats continuously across this range with respect to both biological (7)(8)(9) and behavioral (10,11) phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Genetic and Environmental Influences on Self-Reported Cognitive Functioning: Associations of Diverse Measures of Stress across the FMR1 CGG Repeat Range

Maltman

DaWalt

Hong

et al. 2020

Preprint

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Background: The FMR1 gene is essential for neural development and healthy synaptic function. The modal number of CGG repeats in FMR1 is 30, but the range is large with the reported copy number extending down to as few as 6 CGGs and up to over 200 CGGs. Prior work suggests that behavioral phenotypes, including cognitive function, may vary along the continuum of the FMR1 CGG repeat range. Stress also negatively influences cognitive function; however, it is not known whether FMR1-related variability (i.e., CGG repeat length), in addition to stress, independently influences cognitive function across the CGG range. Methods: Participants included 1275 mothers who had between 18 and 123 CGG repeats. Participants completed self-report measures of executive function (BRIEF-A), memory, subjective stress (i.e., perceived stress), and objective stress (i.e., number of life events, parenting a child with a disability). Stress and CGG repeat length were examined as predictors of self-reported executive function and memory difficulty. Results: Each measure of stress (i.e., perceived stress, life events, and parenting a child with a disability) significantly predicted greater self-reported difficulties in executive function and the likelihood of memory problems, net of age and level of education. Additionally, above and beyond stress effects, CGG repeat number significantly predicted executive functioning and memory difficulties. Conclusions: These findings suggest that CGG repeat length confers independent contributions to self-reported executive function difficulty and memory problems over and above indices of stress, suggesting additive effects of genetic variation and environmental exposure.

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Prevalence and predictors of subjective memory complaints in adult male carriers of the FMR1 premutation

Cited by 7 publications

References 38 publications

Clinical and molecular correlates in fragile X premutation females

Clinical and molecular correlates in fragile X premutation females

The Phenotypic Profile Associated With the FMR1 Premutation in Women: An Investigation of Clinical-Behavioral, Social-Cognitive, and Executive Abilities

Genetic and Environmental Influences on Self-Reported Cognitive Functioning: Associations of Diverse Measures of Stress across the FMR1 CGG Repeat Range

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