Fragile X Syndrome Testing and the Limitations Associated with Current Maternal Cell Contamination Testing Strategies
Philippa A. Dryland
Diagnostic Genetics, Lab Plus, Auckland City Hospital, P.O.Box 110031, Auckland 1148, New Zealand
Annet Damhuis
Diagnostic Genetics, Lab Plus, Auckland City Hospital, P.O.Box 110031, Auckland 1148, New Zealand
Douglas I. Rosendale
The New Zealand Institute for Plant and Food Research Ltd, Private Bag 11600, Palmerston North 4442, New Zealand
Kimberley Hughes
Diagnostic Genetics, Lab Plus, Auckland City Hospital, P.O.Box 110031, Auckland 1148, New Zealand
Elaine Doherty
Diagnostic Genetics, Lab Plus, Auckland City Hospital, P.O.Box 110031, Auckland 1148, New Zealand.
Donald R. Love *
Diagnostic Genetics, Lab Plus, Auckland City Hospital, P.O.Box 110031, Auckland 1148, New Zealand
*Author to whom correspondence should be addressed.
Abstract
Aims: To assess the level of maternal cell contamination (MCC) that can be detected in the molecular determination of triplet repeat expansions in the FMR1 gene.
Place and Duration of Study: Department of Diagnostic Genetics, LabPLUS, Auckland City Hospital, Auckland, New Zealand, between June 2013 and July 2015.
Methodology: We assessed the sensitivity of a fluorescence-based assay for determining the number of CGG repeats in the FMR1 gene in a simulated MCC using spiked samples of known concentrations. This assay was applied to a prenatal case to resolve the question as to whether the CGG alleles detected in the fetal sample were inherited or due to MCC.
Results: The simulated MCC study showed that detection levels range from 0.5% to as low as 0.1%.
Conclusion: Collectively, our data support the view that future MCC guidelines should address the need for increased MCC testing sensitivity to accompany Fragile X syndrome prenatal testing.
Keywords: Fragile X syndrome, maternal cell contamination, trinucleotide repeats.