Journal article
Relationships between age and epi-genotype of the FMR1 exon 1/intron 1 boundary are consistent with non-random X-chromosome inactivation in FM individuals, with the selection for the unmethylated state being most significant between birth and puberty
DE Godler, Y Inaba, EZ Shi, C Skinner, QM Bui, D Francis, DJ Amor, JL Hopper, DZ Loesch, RJ Hagerman, CE Schwartz, HR Slater
Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2013
DOI: 10.1093/hmg/ddt002
Abstract
Methylation of the fragile X-related epigenetic element 2 (FREE2) located on the exon 1/intron 1 boundary of the FMR1 gene is related to FMRP expression and cognitive impairment in full mutation (FM; CGG>200) individuals. We examined the relationship between age, the size of the FMR1 CGG expansion and the methylation output ratio (MOR) at 12 CpG sites proximal to the exon 1/intron 1 boundary using FREE2 MALDI-TOF MS. The patient cohort included 119 males and 368 females, i.e. 121 healthy controls (CGG<40), 176 premutation (CGG 55-170) and 190 FM (CGG 213-2000). For all CpG units examined, FM males showed a significantly elevated MOR compared with that in hypermethylated FM females. In FM mal..
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Awarded by National Institute of Child Health and Human Development
Funding Acknowledgements
[ "D.E.G. is an inventor on a patent related to the technology described in this article. R.J.H. has received grant funding from Roche, Novartis, Seaside Therapeutics, Forest and Curemark for treatment studies in fragile X syndrome or autism. She has also consulted with Novartis regarding treatment of fragile X syndrome. The other authors declare that they have no conflicts of interest.", "This work was supported by the Victorian Government's Operational Infrastructure Support Program, NHMRC development grant (No 1017263 to H. R. S. and D. E. G.), E. W. Al Thrasher Award, USA (to H. R. S. and D. E. G.), Martin & E. H. Flack Trust, Australia (to H. R. S. and D. E. G.), National Institute of Child Health and Human Development grant, USA (HD36071 to D.Z.L. and R.J.H.) and in part by a grant from the South Carolina Department of Disabilities and Special Needs (SCDDSN). This study was also supported by NHMRC project grant (No 104299 to H. R. S. and D.E.G.)." ]