Guidelines for molecular karyotyping in constitutional genetic diagnosis.
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.
Vermeesch
Joris Robert
JR
Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium. Joris.Vermeesh@med.kuleuven.de
Fiegler
Heike
H
de Leeuw
Nicole
N
Szuhai
Karoly
K
Schoumans
Jacqueline
J
Ciccone
Roberto
R
Speleman
Frank
F
Rauch
Anita
A
Clayton-Smith
Jill
J
Van Ravenswaaij
Conny
C
Sanlaville
Damien
D
Patsalis
Philippos C
PC
Firth
Helen
H
Devriendt
Koen
K
Zuffardi
Orsetta
O
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