title: A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors.
abstract: OBJECTIVE
  To evaluate the clinical utility of chromosomal microarrays for prenatal diagnosis by a prospective study of fetuses with abnormalities detected on ultrasound.
  
  
  METHODS
  Patients referred for prenatal diagnosis due to ultrasound anomalies underwent analysis by array comparative genomic hybridization as the first-tier diagnostic test.
  
  
  RESULTS
  A total of 383 prenatal samples underwent analysis by array comparative genomic hybridization. Array analysis revealed causal imbalances in a total of 9.6% of patients (n = 37). Submicroscopic copy-number variations were detected in 2.6% of patients (n = 10/37), and arrays added valuable information over conventional karyotyping in 3.9% of patients (n = 15/37). We highlight a novel advantage of arrays; a 500-kb paternal insertional translocation is the likely driver of a de novo unbalanced translocation, thus improving recurrence risk calculation in this family. Variants of uncertain significance were revealed in 1.6% of patients (n = 6/383).
  
  
  CONCLUSIONS
  We demonstrate the added value of chromosomal microarrays for prenatal diagnosis in the presence of ultrasound anomalies. We advocate reporting back only copy-number variations with known pathogenic significance. Although this approach might be considered opposite to the ideal of full reproductive autonomy of the parents, we argue why providing all information to parents may result in a false sense of autonomy.
authors.affiliation: Centre for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Paul Daniel
authors.initials: PD
authors.lastname: Brady
authors.affiliation: Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Delle Chiaie
authors.affiliation: Centre for Biomedical Ethics and Law, Faculty of Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Christenhusz
authors.affiliation: Centre for Biomedical Ethics and Law, Faculty of Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Dierickx
authors.affiliation: Centre for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Van Den Bogaert
authors.affiliation: Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Menten
authors.affiliation: Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Janssens
authors.affiliation: Department of Obstetrics and Gynaecology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Defoort
authors.affiliation: Department of Obstetrics and Gynaecology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Roets
authors.affiliation: Department of Obstetrics and Gynaecology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Sleurs
authors.affiliation: Center for Medical Genetics, Universitair Ziekenhuis Brussels, Vrije Universiteit Brussels, Brussels, Belgium.
authors.forename: Kathelijn
authors.initials: K
authors.lastname: Keymolen
authors.affiliation: 1] Department of Development and Regeneration, Unit Pregnancy, Foetus and Newborn, KU Leuven, Leuven, Belgium [2] Department of Obstetrics and Gynaecology, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: De Catte
authors.affiliation: 1] Department of Development and Regeneration, Unit Pregnancy, Foetus and Newborn, KU Leuven, Leuven, Belgium [2] Department of Obstetrics and Gynaecology, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Deprest
authors.affiliation: Centre for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Thomy
authors.initials: T
authors.lastname: de Ravel
authors.affiliation: Centre for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Hilde
authors.initials: H
authors.lastname: Van Esch
authors.affiliation: Centre for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Fryns
authors.affiliation: Centre for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
authors.affiliation: Centre for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Joris Robert
authors.initials: JR
authors.lastname: Vermeesch
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics*; D015193:Chorionic Villi Sampling; D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D008297:Male; D009030:Mosaicism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D011446:Prospective Studies; D012307:Risk Factors; D016216:Ultrasonography, Prenatal