journal contribution
posted on 2025-10-28, 03:34 authored by Emma BakerEmma Baker, M Arpone, C Kraan, M Bui, C Rogers, M Field, L Bretherton, L Ling, A Ure, J Cohen, MF Hunter, L Santa María, V Faundes, B Curotto, P Morales, C Trigo, I Salas, A Alliende, DJ Amor, DE Godler 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.<p></p>
Funding
This study was supported by the Victorian Government’s Operational Infrastructure Support Program, with the salaries supported by NHMRC project grants (no. 1049299 and no. 1103389 to D.E.G; and no. 1103389 to C.M.K.); Murdoch Children’s Research Institute, Royal Children’s Hospital Foundation (D.E.G.); Next Generation Clinical Researchers Program - Career Development Fellowship, funded by the Medical Research Future Fund (MRF1141334 to D.E.G.); and the Financial Markets Foundation for Children (Australia) (no. 2017 – 361 to D.E.G. C.M.K. and D.J.A.); M.J.F. and C.R. were supported by the Genetics of Learning Disability (GOLD) Service. M.A. was supported by an Australian Postgraduate Award, the International Postgraduate Research Scholarships (IPRS) and the Research Training Program Fee offset scholarship funded by the Australian Government and awarded by the University of Melbourne, and in part by the Diagnosis and Development group of the Murdoch Children’s Research Institute.
History
Publication Date
2020-07-16Journal
Scientific ReportsVolume
10Article Number
11701Pagination
8p.Publisher
Springer NatureISSN
2045-2322Rights Statement
© The Author(s) 2020.
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
