Objective: We evaluated both clinical and laboratory aspects of our new strategy offering quantitative fluorescence (QF)-PCR followed by non-targeted whole genome 250K single-nucleotide polymorphism array analysis instead of routine karyotyping for prenatal diagnosis of fetuses with structural anomalies. Methods: Upon the detection of structural fetal anomalies, parents were offered a choice between QF-PCR and 250K single-nucleotide polymorphism array analysis (QF/array) or QF-PCR and routine karyotyping (QF/karyo). Results: Two hundred twenty fetal samples were included. In 153/220 cases (70%), QF/array analysis was requested. In 35/153 (23%), an abnormal QF-PCR result was found. The remaining samples were analyzed by array, which revealed clinically relevant aberrations, including two known microdeletions, in 5/118 cases. Inherited copy number variants were detected in 11/118 fetuses, copy number variants with uncertain clinical relevance in 3/118 and homozygous stretches in 2/118. In 67/220 (30%) fetuses, QF/karyo was requested: 23/67 (34%) were abnormal with QF-PCR, and in 3/67, an abnormal karyotype was found. Conclusion: Even though QF/array does not reveal a high percentage of submicroscopic aberrations in fetuses with unselected structural anomalies, it is preferred over QF/karyo, as it provides a whole genome scan at high resolution, without additional tests needed and with a low chance on findings not related to the ultrasound anomalies.

Array CGH, General cytogenetics, Genetic counselling, Non-targeted, SNP array, Whole genome
dx.doi.org/10.1002/pd.2948, hdl.handle.net/1765/63077
Prenatal Diagnosis
Department of Gynaecology & Obstetrics

Faas, B.H.W, Feenstra, I, Eggink, A.J, Kooper, A.J.A, Pfundt, R, van Vugt, J.M.G, & de Leeuw, N. (2012). Non-targeted whole genome 250K SNP array analysis as replacement for karyotyping in fetuses with structural ultrasound anomalies: Evaluation of a one-year experience. Prenatal Diagnosis, 32(4), 362–370. doi:10.1002/pd.2948