title: Guidelines for molecular karyotyping in constitutional genetic diagnosis.
abstract: Array-based whole genome investigation or molecular karyotyping enables the genome-wide detection of submicroscopic imbalances. Proof-of-principle experiments have demonstrated that molecular karyotyping outperforms conventional karyotyping with regard to detection of chromosomal imbalances. This article identifies areas for which the technology seems matured and areas that require more investigations. Molecular karyotyping should be part of the genetic diagnostic work-up of patients with developmental disorders. For the implementation of the technique for other constitutional indications and in prenatal diagnosis, more research is appropriate. Also, the article aims to provide best practice guidelines for the application of array comparative genomic hybridisation to ensure both technical and clinical quality criteria that will optimise and standardise results and reports in diagnostic laboratories. In short, both the specificity and the sensitivity of the arrays should be evaluated in every laboratory offering the diagnostic test. Internal and external quality control programmes are urgently needed to evaluate and standardise the test results between laboratories.
authors.affiliation: Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium. Joris.Vermeesh@med.kuleuven.de
authors.forename: Joris Robert
authors.initials: JR
authors.lastname: Vermeesch
authors.forename: Heike
authors.initials: H
authors.lastname: Fiegler
authors.forename: Nicole
authors.initials: N
authors.lastname: de Leeuw
authors.forename: Karoly
authors.initials: K
authors.lastname: Szuhai
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schoumans
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccone
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: Conny
authors.initials: C
authors.lastname: Van Ravenswaaij
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.forename: Philippos C
authors.initials: PC
authors.lastname: Patsalis
authors.forename: Helen
authors.initials: H
authors.lastname: Firth
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
mesh_terms: D002648:Child; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D023281:Genomics / Q000941:ethics / Q000379:methods; D006801:Humans; D007621:Karyotyping / Q000379:methods; D009693:Nucleic Acid Hybridization / Q000941:ethics / Q000235:genetics / Q000379:methods; D017410:Practice Guidelines as Topic / Q000592:standards; D011296:Prenatal Diagnosis / Q000941:ethics / Q000379:methods / Q000592:standards