A Challenging Prenatal QF-PCR Rapid Aneuploidy Test Result Caused by a Maternally Inherited Triplication within Chromosome Xq26.2

Abstract

The aim of this study was to investigate the origin of the biallelic trisomic amplification pattern of the X chromosome microsatellite marker DXS1187 in an otherwise normal male fetus, identified on routine rapid aneuploidy detection (RAD) testing by quantitative fluorescent-polymerase chain reaction (QF-PCR). Amniocentesis was performed on a 35-year-old female at 15 weeks, 2 days gestation for a positive first trimester screen. QF-PCR, metaphase FISH, and chromosomal microarray were carried out on both maternal and fetal DNA. Fetal QF-PCR showed a biallelic trisomic pattern for the X chromosome microsatellite marker DXS1187, with an otherwise normal male amplification pattern at all other sex chromosome markers. Chromosome analysis performed on cultured amniocytes showed a normal male karyotype. Chromosome microarray analysis identified a maternally inherited 304-kb copy number triplication within chromosome Xq26.2 encompassing the DXS1187 marker. The maternally inherited X chromosome harbors an apparently tandem 304-kb triplication that overlaps the DXS1187 marker. As the triplicated region is devoid of clinically relevant genes, it was considered as likely benign in the fetus. Postnatal follow-up reported a healthy male newborn. To our knowledge, this is a unique case demonstrating a "benign" copy number imbalance involving the DXS1187 marker detected by prenatal QF-PCR RAD.

Keywords: Prenatal diagnosis; QF-PCR; Triplication; Xq26.2.