title: Clinical utility of chromosomal microarray analysis in invasive  prenatal diagnosis.
abstract: Novel methodologies for detection of chromosomal abnormalities have been made available in the recent years but their clinical utility in prenatal settings is still unknown. We have conducted a comparative study of currently available methodologies for detection of chromosomal abnormalities after invasive prenatal sampling.A multicentric collection of a 1-year series of fetal samples with indication for prenatal invasive sampling was simultaneously evaluated using three screening methodologies: (1) karyotype and quantitative fluorescent polymerase chain reaction (QF-PCR), (2) two panels of multiplex ligation-dependent probe amplification (MLPA), and (3) chromosomal microarray-based analysis (CMA) with a targeted BAC microarray. A total of 900 pregnant women provided informed consent to participate (94% acceptance rate). Technical performance was excellent for karyotype, QF-PCR, and CMA (~1% failure rate), but relatively poor for MLPA (10% failure). Mean turn-around time (TAT) was 7 days for CMA or MLPA, 25 for karyotype, and two for QF-PCR, with similar combined costs for the different approaches. A total of 57 clinically significant chromosomal aberrations were found (6.3%), with CMA yielding the highest detection rate (32% above other methods). The identification of variants of uncertain clinical significance by CMA (17, 1.9%) tripled that of karyotype and MLPA, but most alterations could be classified as likely benign after proving they all were inherited. High acceptability, significantly higher detection rate and lower TAT, could justify the higher cost of CMA and favor targeted CMA as the best method for detection of chromosomal abnormalities in at-risk pregnancies after invasive prenatal sampling.
authors: qGenomics Laboratory, Doctor Aiguader, 88, 08003 Barcelona, Spain.
authors: Lluís
authors: L
authors: Armengol
authors: Julián
authors: J
authors: Nevado
authors: Clara
authors: C
authors: Serra-Juhé
authors: Alberto
authors: A
authors: Plaja
authors: Carmen
authors: C
authors: Mediano
authors: Fe Amalia
authors: FA
authors: García-Santiago
authors: Manel
authors: M
authors: García-Aragonés
authors: Olaya
authors: O
authors: Villa
authors: Elena
authors: E
authors: Mansilla
authors: Cristina
authors: C
authors: Preciado
authors: Luis
authors: L
authors: Fernández
authors: María
authors: M
authors: Ángeles Mori
authors: Lidia
authors: L
authors: García-Pérez
authors: Pablo Daniel
authors: PD
authors: Lapunzina
authors: Luis Alberto
authors: LA
authors: Pérez-Jurado
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000235:genetics*; D005260:Female; D006801:Humans; D059785:Karyotype; D020411:Oligonucleotide Array Sequence Analysis / Q000191:economics; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000191:economics / Q000379:methods*; D012680:Sensitivity and Specificity