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dc.contributor.authorGodler, DE
dc.contributor.authorTassone, F
dc.contributor.authorLoesch, DZ
dc.contributor.authorTaylor, AK
dc.contributor.authorGehling, F
dc.contributor.authorHagerman, RJ
dc.contributor.authorBurgess, T
dc.contributor.authorGanesamoorthy, D
dc.contributor.authorHennerich, D
dc.contributor.authorGordon, L
dc.contributor.authorEvans, A
dc.contributor.authorChoo, KH
dc.contributor.authorSlater, HR
dc.identifierpii: ddq037
dc.identifier.citationGodler, D. E., Tassone, F., Loesch, D. Z., Taylor, A. K., Gehling, F., Hagerman, R. J., Burgess, T., Ganesamoorthy, D., Hennerich, D., Gordon, L., Evans, A., Choo, K. H. & Slater, H. R. (2010). Methylation of novel markers of fragile X alleles is inversely correlated with FMRP expression and FMR1 activation ratio. HUMAN MOLECULAR GENETICS, 19 (8), pp.1618-1632.
dc.descriptionC - Journal Articles
dc.description.abstractThe fragile X syndrome (FXS) is caused by silencing of the fragile X mental retardation gene (FMR1) and the absence of its product, fragile X mental retardation protein (FMRP), resulting from CpG island methylation associated with large CGG repeat expansions (more than 200) termed full mutation (FM). We have identified a number of novel epigenetic markers for FXS using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), naming the most informative fragile X-related epigenetic element 1 (FREE1) and 2 (FREE2). Methylation of both regions was correlated with that of the FMR1 CpG island detected using Southern blot (FREE1 R = 0.97; P < 0.00001, n = 23 and FREE2 R = 0.93; P < 0.00001, n = 23) and negatively correlated with lymphocyte expression of FMRP (FREE1 R = -0.62; P = 0.01, n = 15 and FREE2 R = -0.55; P = 0.03, n = 15) in blood of partially methylated 'high functioning' FM males. In blood of FM carrier females, methylation of both markers was inversely correlated with the FMR1 activation ratio (FREE1 R = -0.93; P < 0.0001, n = 12 and FREE2 R = -0.95; P < 0.0001, n = 9). In a sample set of 49 controls, 18 grey zone (GZ 40-54 repeats), 22 premutation (PM 55-170 repeats) and 22 (affected) FXS subjects, the FREE1 methylation pattern was consistent between blood and chorionic villi as a marker of methylated FM alleles and could be used to differentiate FXS males and females from controls, as well as from carriers of GZ/PM alleles, but not between GZ and PM alleles and controls. Considering its high-throughput and specificity for pathogenic FM alleles, low cost and minimal DNA requirements, FREE MALDI-TOF MS offers a unique tool in FXS diagnostics and newborn population screening.
dc.subjectNeurology and Neuromuscular Diseases; Expanding Knowledge in the Medical and Health Sciences
dc.titleMethylation of novel markers of fragile X alleles is inversely correlated with FMRP expression and FMR1 activation ratio
dc.typeJournal Article
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMedicine - Royal Melbourne Hospital
melbourne.source.titleHUMAN MOLECULAR GENETICS
melbourne.contributor.authorChoo, Kong
melbourne.contributor.authorSlater, Howard
melbourne.contributor.authorEvans, Andrew
melbourne.contributor.authorGodler, David
melbourne.contributor.authorGANESAMOORTHY, DEVIKA
melbourne.contributor.authorGordon, Lavinia
melbourne.accessrightsAccess this item via the Open Access location

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