Journal article

Fragile X-related element 2 methylation analysis may provide a suitable option for inclusion of fragile X syndrome and/or sex chromosome aneuploidy into newborn screening: a technical validation study

Yoshimi Inaba, Amy S Herlihy, Charles E Schwartz, Cindy Skinner, Quang M Bui, Joanna Cobb, Elva Z Shi, David Francis, Alison Arvaj, David J Amor, Kate Pope, Tiffany Wotton, Jonathan Cohen, Jacqueline K Hewitt, Randi J Hagerman, Sylvia A Metcalfe, John L Hopper, Danuta Z Loesch, Howard R Slater, David E Godler



PURPOSE: We show that a novel fragile X-related epigenetic element 2 FMR1 methylation test can be used along with a test for sex-determining region Y (SRY) to provide the option of combined fragile X syndrome and sex chromosome aneuploidy newborn screening. METHODS: Fragile X-related epigenetic element 2, SRY, and FMR1 CGG repeat analyses were performed on blood and saliva DNA, and in adult and newborn blood spots. The cohort consisted of 159 controls (CGG <40), 187 premutation (CGG 56-170), and 242 full-mutation (CGG ~200-2,000) males and females, 106 sex chromosome aneuploidy individuals, and 151 cytogenetically normal controls. RESULTS: At the 0.435 threshold, fragile X-related epigenetic..

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Awarded by NHMRC development grant

Awarded by National Institute of Child Health and Human Development grant, USA


Funding Acknowledgements

We thank the study participants and their families for their contribution. We also thank Alison Archibald for recruitment and collection of saliva DNA samples from male and female controls, and James Pitt, Nick Tzanakos, and other members of the Newborn Screening Laboratory at the Victorian Clinical Genetics Services for retrieval of residual newborn blood spots. We thank Benjamin Ong from the Sequenom Platform Facility at the Murdoch Chlidrens Research Institute for his assistance with MALDI-TOF MS application. We also thank Christopher Boyer of Bio-Link Australia Pty. for critical review of the manuscript. This work was supported by the Victorian government's Operational Infrastructure Support Program, an NHMRC development grant (no. 1017263 to H. R. S. and D. E. G.), the E.W. Al Thrasher Award, USA (to H. R. S. and D. E. G.), a National Institute of Child Health and Human Development grant, USA (HD36071 to D.Z.L. and R.J.H.), Andrology Australia, and Monash University and in part by a grant from the South Carolina Department of Disabilities and Special Needs.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 no conflict of interest.