title: A new direction for prenatal chromosome microarray testing: software-targeting for detection of clinically significant chromosome imbalance without equivocal findings.
abstract: Purpose. To design and validate a prenatal chromosomal microarray testing strategy that moves away from size-based detection thresholds, towards a more clinically relevant analysis, providing higher resolution than G-banded chromosomes but avoiding the detection of copy number variants (CNVs) of unclear prognosis that cause parental anxiety. Methods. All prenatal samples fulfilling our criteria for karyotype analysis (n = 342) were tested by chromosomal microarray and only CNVs of established deletion/duplication syndrome regions and any other CNV >3 Mb were detected and reported. A retrospective full-resolution analysis of 249 of these samples was carried out to ascertain the performance of this testing strategy. Results. Using our prenatal analysis, 23/342 (6.7%) samples were found to be abnormal. Of the remaining samples, 249 were anonymized and reanalyzed at full-resolution; a further 46 CNVs were detected in 44 of these cases (17.7%). None of these additional CNVs were of clear clinical significance. Conclusion. This prenatal chromosomal microarray strategy detected all CNVs of clear prognostic value and did not miss any CNVs of clear clinical significance. This strategy avoided both the problems associated with interpreting CNVs of uncertain prognosis and the parental anxiety that are a result of such findings.
authors.affiliation: Cytogenetics, Guy's & St Thomas' NHS Foundation Trust , London , UK.
authors.forename: Joo Wook
authors.initials: JW
authors.lastname: Ahn
authors.affiliation: Cytogenetics, GSTS Pathology , London , UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Bint
authors.affiliation: Clinical Genetics, Guy's & St Thomas' NHS Foundation Trust , London , UK.
authors.forename: Melita D
authors.initials: MD
authors.lastname: Irving
authors.affiliation: Fetal Medicine Unit, Guy's & St Thomas' NHS Foundation Trust , London , UK.
authors.forename: Phillipa M
authors.initials: PM
authors.lastname: Kyle
authors.affiliation: Fetal Medicine Unit, Medway Maritime Hospital , Kent , UK.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Akolekar
authors.affiliation: Clinical Genetics, Guy's & St Thomas' NHS Foundation Trust , London , UK.
authors.forename: Shehla N
authors.initials: SN
authors.lastname: Mohammed
authors.affiliation: Cytogenetics, Guy's & St Thomas' NHS Foundation Trust , London , UK ; King's College , London , UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mackie Ogilvie
keywords: Array CGH; CMA; Prenatal; Prenatal testing; Software targeting; VUS