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. 2020 Mar:139:105511.
doi: 10.1016/j.bandc.2019.105511. Epub 2019 Dec 27.

Inhibition deficits are modulated by age and CGG repeat length in carriers of the FMR1 premutation allele who are mothers of children with fragile X syndrome

Jessica Klusek  1 , Jinkuk Hong  2 , Audra Sterling  3 , Elizabeth Berry-Kravis  4 , Marsha R Mailick  5
Affiliations

Inhibition deficits are modulated by age and CGG repeat length in carriers of the FMR1 premutation allele who are mothers of children with fragile X syndrome

Jessica Klusek et al. Brain Cogn. 2020 Mar.

Abstract

Individuals who carry a premutation (PM) allele on the FMR1 gene may experience executive limitations associated with their genetic status, including inhibition deficits. However, poor understanding of individualized risk factors has limited clinical management of this group, particularly in mothers who carry the PM allele who have children with fragile X syndrome (FXS). The present study examined CGG repeat length and age as factors that may account for variable expressivity of inhibition deficits. Participants were 134 carriers of the PM allele who were mothers of children with FXS. Inhibition skills were measured using both self-report and direct behavioral assessments. Increased vulnerability for inhibition deficits was observed at mid-range CGG lengths of approximately 80-100 repeats, with some evidence of a second zone of vulnerability occurring at approximately 130-140 CGG repeats. Risk associated with the genotype also became more pronounced with older age. This study identifies personalized risk factors that may be used to tailor the clinical management of executive deficits in carriers of the PM allele. Inhibition deficits may contribute to poor outcomes in carriers of the PM allele and their families, particularly in midlife and early old age, and clinical monitoring may be warranted.

Keywords: FMR1 premutation; age effects; executive dysfunction; fragile X premutation carrier; mid-range CGG.

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Figures

Figure 1.
Figure 1.. Curvilinear association between CGG repeat length and the Hayling latency score
Note. Model-predicted values are presented, controlling for education level. Longer latency on the Hayling reflects poorer inhibition skills.
Figure 2.
Figure 2.. Curvilinear association between CGG repeat length and the BRIEF-A Inhibit subscale
Note. Model-predicted values are presented, controlling for education level. Higher t-scores on the Inhibit subscale reflect poorer inhibition skills.
Figure 3.
Figure 3.. Effect of age on the Hayling latency score
Note. Model-predicted values are presented, controlling for education level. Longer latency on the Hayling reflects poorer inhibition skills.
See this image and copyright information in PMC

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