Journal article

Significantly Elevated FMR1 mRNA and Mosaicism for Methylated Premutation and Full Mutation Alleles in Two Brothers with Autism Features Referred for Fragile X Testing

Michael Field, Tracy Dudding-Byth, Marta Arpone, Emma K Baker, Solange M Aliaga, Carolyn Rogers, Chriselle Hickerton, David Francis, Dean G Phelan, Elizabeth E Palmer, David J Amor, Howard Slater, Lesley Bretherton, Ling Ling, David E Godler



Although fragile X syndrome (FXS) is caused by a hypermethylated full mutation (FM) expansion with ≥200 cytosine-guanine-guanine (CGG) repeats, and a decrease in FMR1 mRNA and its protein (FMRP), incomplete silencing has been associated with more severe autism features in FXS males. This study reports on brothers (B1 and B2), aged 5 and 2 years, with autistic features and language delay, but a higher non-verbal IQ in comparison to typical FXS. CGG sizing using AmplideX PCR only identified premutation (PM: 55-199 CGGs) alleles in blood. Similarly, follow-up in B1 only revealed PM alleles in saliva and skin fibroblasts; whereas, an FM expansion was detected in both saliva and buccal DNA of B2...

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Awarded by Financial Markets Foundation for Children (Australia) (FMFC)

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by Next Generation Clinical Researchers Program-Career Development Fellowship - Medical Research Future Fund

Funding Acknowledgements

This work was funded by The Victorian Government's Operational Infrastructure Support Program, Murdoch Children's Research Institute, Royal Children's Hospital Foundation, Martin & E.H. Flack Trust, Pierce Armstrong Trust, Financial Markets Foundation for Children (Australia) (FMFC; grant number: 2017-361), and the National Health and Medical Research Council (NHMRC; project grant numbers: 1049299 and 1103389). D.E.G. was supported by the Next Generation Clinical Researchers Program-Career Development Fellowship Funded by the Medical Research Future Fund (grant number 1141334). M.A. was supported by the International Postgraduate Research Scholarship (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.