Fragile X Syndrome Testing and the Limitations Associated with Current Maternal Cell Contamination Testing Strategies

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.