Noninvasive prenatal genetic testing for fetal aneuploidy detects maternal trisomy X.

Trisomy X is a sex chromosomal abnormality with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1000 female births. There is considerable variation in the phenotype, from asymptomatic and very mildly affected to significant physical and psychological features, leading only 10% of diagnosis ratio for those individuals with trisomy X. Current prenatal diagnosis of trisomy X relies on invasive prenatal tests such as karyotyping analysis. Although such tests allow accurate diagnosis, wide clinical use is limited by its complex operations and invasive nature with a 0.5% to 1% of procedure-related miscarriage. Recently, a newmethod based on massively parallel sequencing for cell-free DNA in maternal plasma was developed to detect fetal trisomy disorders. A rapid response statement from a committee on behalf of the Board of the International Society for Prenatal Diagnosis showed that the test currently available is only for fetal trisomy 21 and trisomy 18, which constitutes only about half of the fetal aneuploidy that would be identified through amniocentesis or CVS. Prior studies have shown that this massively parallel sequencing based noninvasive fetal trisomy test (the NIFTY test, which has no relationship with the ‘NIFTY’ trial on noninvasive prenatal diagnosis that was sponsored by the US National Institutes of Health) can not only detect trisomy 21 and trisomy 18, but also sex chromosomal aneuploidies. However, the effect of the maternal genetic background on the performance of the NIFTY test is not clear. Here we present a case in which maternal chromosome X materials affect the performance of the NIFTY. This case may provide a useful complement for the clinical application of the NIFTY test.