title: High-resolution chromosomal microarrays in prenatal diagnosis significantly increase diagnostic power.
abstract: OBJECTIVE
  The objective of this study was to determine for the first time the reliability and the diagnostic power of high-resolution microarray testing in routine prenatal diagnostics.
  
  
  METHODS
  We applied high-resolution chromosomal microarray testing in 464 cytogenetically normal prenatal samples with any indication for invasive testing.
  
  
  RESULTS
  High-resolution testing revealed a diagnostic yield of 6.9% and 1.6% in cases of fetal ultrasound anomalies and cases of advanced maternal age (AMA), respectively, which is similar to previous studies using low-resolution microarrays. In three (0.6%) additional cases with an indication of AMA, an aberration in susceptibility risk loci was detected. Moreover, one case (0.2%) showed an X-linked aberration in a female fetus, a finding relevant for future family planning. We found the rate of cases, in which the parents had to be tested for interpretation of unreported copy number variants (3.7%), and the rate of remaining variants of unknown significance (0.4%) acceptably low. Of note, these findings did not cause termination of pregnancy after expert genetic counseling. The 0.4% rate of confined placental mosaicism was similar to that observed by conventional karyotyping and notably involved a case of placental microdeletion.
  
  
  CONCLUSIONS
  High-resolution prenatal microarray testing is a reliable technique that increases diagnostic yield by at least 17.3% when compared with conventional karyotyping, without an increase in the frequency of variants of uncertain significance.
authors.affiliation: Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Oneda
authors.forename: Rosa
authors.initials: R
authors.lastname: Baldinger
authors.forename: Regina
authors.initials: R
authors.lastname: Reissmann
authors.forename: Irina
authors.initials: I
authors.lastname: Reshetnikova
authors.forename: Pavel
authors.initials: P
authors.lastname: Krejci
authors.forename: Rahim
authors.initials: R
authors.lastname: Masood
authors.forename: Nicole
authors.initials: N
authors.lastname: Ochsenbein-Kölble
authors.forename: Deborah
authors.initials: D
authors.lastname: Bartholdi
authors.forename: Katharina
authors.initials: K
authors.lastname: Steindl
authors.forename: Denise
authors.initials: D
authors.lastname: Morotti
authors.forename: Marzia
authors.initials: M
authors.lastname: Faranda
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baumer
authors.forename: Reza
authors.initials: R
authors.lastname: Asadollahi
authors.forename: Pascal
authors.initials: P
authors.lastname: Joset
authors.forename: Dunja
authors.initials: D
authors.lastname: Niedrist
authors.forename: Christian
authors.initials: C
authors.lastname: Breymann
authors.forename: Gundula
authors.initials: G
authors.lastname: Hebisch
authors.forename: Margaret
authors.initials: M
authors.lastname: Hüsler
authors.forename: René
authors.initials: R
authors.lastname: Mueller
authors.forename: Elke
authors.initials: E
authors.lastname: Prentl
authors.forename: Josef
authors.initials: J
authors.lastname: Wisser
authors.forename: Roland
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007621:Karyotyping / Q000379:methods; D008423:Maternal Age; D046228:Microarray Analysis / Q000379:methods*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D015203:Reproducibility of Results