FMR1 mRNA from full mutation alleles is associated with ABC-CFX scores in males with fragile X syndrome

Emma K. Baker, Marta Arpone, Claudine Kraan, Minh Bui, Carolyn Rogers, Michael Field, Lesley Bretherton, Ling Ling, Alexandra Ure, Jonathan Cohen, Matthew F. Hunter, Lorena Santa María, Victor Faundes, Bianca Curotto, Paulina Morales, Cesar Trigo, Isabel Salas, Angelica Alliende, David J. Amor, David E. Godler

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Fragile X syndrome (FXS) is caused by a hypermethylated full mutation (FM) expansion with ≥ 200 CGG repeats, and a decrease in FMR1 mRNA and its protein. However, incomplete silencing from FM alleles has been associated with more severe autism features in FXS males. This study compared scores on the Aberrant Behavior Checklist-Community-FXS version (ABC-CFX) in 62 males affected with FXS (3 to 32 years) stratified based on presence or absence of mosaicism and/or FMR1 mRNA silencing. Associations between ABC-CFX subscales and FMR1 mRNA levels, assessed using real-time PCR relative standard curve method, were also examined. The FXS group mosaic for premutation (PM: 55–199 CGGs) and FM alleles had lower irritability (p = 0.014) and inappropriate speech (p < 0.001) scores compared to males with only FM alleles and complete loss of FMR1 mRNA. The PM/FM mosaic group also showed lower inappropriate speech scores compared to the incomplete silencing (p = 0.002) group. Increased FMR1 mRNA levels were associated with greater irritability (p < 0.001), and lower health-related quality of life scores (p = 0.004), but only in the incomplete silencing FM-only group. The findings suggest that stratification based on CGG sizing and FMR1 mRNA levels may be warranted in future research and clinical trials utilising ABC-CFX subscales as outcome measures.

Original languageEnglish
Article number11701
Number of pages8
JournalScientific Reports
Issue number1
Publication statusPublished - 16 Jul 2020


  • gene expression
  • neurodevelopmental disorders

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