Journal article

Abnormally Methylated FMR1 in Absence of a Detectable Full Mutation in a U.S.A Patient Cohort Referred for Fragile X Testing

CH Hensel, RJ Vanzo, MM Martin, L Ling, SM Aliaga, M Bui, DI Francis, H Twede, MH Field, JW Morison, DJ Amor, DE Godler

Scientific Reports | NATURE PORTFOLIO | Published : 2019

Abstract

In 2016, Methylation-Specific Quantitative Melt Analysis (MS-QMA) on 3,340 male probands increased diagnostic yield from 1.60% to 1.84% for fragile X syndrome (FXS) using a pooling approach. In this study probands from Lineagen (UT, U.S.A.) of both sexes were screened using MS-QMA without sample pooling. The cohorts included: (i) 279 probands with no FXS full mutation (FM: CGG > 200) detected by AmplideX CGG sizing; (ii) 374 negative and 47 positive controls. MS-QMA sensitivity and specificity in controls approached 100% for both sexes. For male probands with no FM detected by standard testing (n = 189), MS-QMA identified abnormal DNA methylation (mDNA) in 4% normal size (NS: < 44 CGGs), 6% ..

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Grants

Awarded by Financial Markets Foundation for Children


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), the National Health and Medical Research Council (NHMRC; project grant numbers: 104299 and 1103389 to D. E.G.). D.E.G. salary was also supported by the Next Generation Clinical Researchers Program - Career Development Fellowship Funded by the Medical Research Future Fund (grant number 1141334). Megan Martin, Rena Vanzo, Hope Twede, and Charles Hensel were employees of Lineagen Inc. (commercial company) and received funding and stock options from Lineagen Inc.