Journal article

Early Detection of Fragile X Syndrome: Applications of a Novel Approach for Improved Quantitative Methylation Analysis in Venous Blood and Newborn Blood Spots

Yoshimi Inaba, Charles E Schwartz, Quang M Bui, Xin Li, Cindy Skinner, Michael Field, Tiffany Wotton, Randi J Hagerman, David Francis, David J Amor, John L Hopper, Danuta Z Loesch, Lesley Bretherton, Howard R Slater, David E Godler



BACKGROUND: Standard fragile X syndrome (FXS) diagnostic tests that target methylation of the fragile X mental retardation 1 (FMR1) CpG island 5' of the CGG expansion can be used to predict severity of the disease in males from birth, but not in females. METHODS: We describe methylation specific-quantitative melt analysis (MS-QMA) that targets 10 CpG sites, with 9 within FMR1 intron 1, to screen for FXS from birth in both sexes. The novel method combines the qualitative strengths of high-resolution melt and the high-throughput, quantitative real-time PCR standard curve to provide accurate quantification of DNA methylation in a single assay. Its performance was assessed in 312 control (CGG <4..

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Awarded by NHMRC Project

Awarded by NHMRC development grant

Funding Acknowledgements

NHMRC Project (grant 1049299), the Victorian Government's Operational Infrastructure Support Program, Murdoch Childrens Research Institute, Royal Children's Hospital Foundation, and the South Carolina Department of Disabilities and Special Needs (SCDDSN); R. Hagerman, Roche, Novartis, Seaside Therapeutics, Forest, and Curemark; D.E. Godler, NHMRC Project (grant 104299), NHMRC development grant (1017263), Martin & E.H. Flack Trust, Australia, and E.W. Al Thrasher Award, USA.