FMR1 mRNA from full mutation alleles is associated with ABC-C-FX scores in males with fragile X syndrome
Author
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Baker, Emma K.
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Arpone, Marta
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Kraan, Claudine
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Bui, Minh
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Rogers, Carolyn
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Field, Michael
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Bretherton, Lesley
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Ling, Ling
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Ure, Alexandra
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Cohen, Jonathan
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Hunter, Matthew F.
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Santa María Vásquez, Lorena
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Faúndes Gómez, Víctor
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Curotto, Bianca
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Morales, Paulina
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Trigo, César
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Salas, Isabel
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Alliende Rodríguez, Angélica
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Amor, David J.
Author
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Godler, David E.
Admission date
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2020-09-30T21:17:11Z
Available date
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2020-09-30T21:17:11Z
Publication date
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2020
Cita de ítem
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Scientific Reports. (2020) 10:11701
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Identifier
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10.1038/s41598-020-68465-6
Identifier
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https://repositorio.uchile.cl/handle/2250/176897
Abstract
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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-C-FX) 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-C-FX 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-C-FX subscales as outcome measures.
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Patrocinador
dc.description.sponsorship
Victorian Government's Operational Infrastructure Support Program
National Health and Medical Research Council of Australia
1049299
1103389
Murdoch Children's Research Institute
Royal Children's Hospital Foundation
Next Generation Clinical Researchers Program - Career Development Fellowship - Medical Research Future Fund
MRF1141334
Financial Markets Foundation for Children (Australia)
2017 - 361
Genetics of Learning Disability (GOLD) Service
Australian Government
International Postgraduate Research Scholarships (IPRS)
Australian Government
University of Melbourne
Diagnosis and Development group of the Murdoch Children's Research Institute