Journal Article

Guidelines for molecular karyotyping in constitutional genetic diagnosis

Schoumans, Jacqueline, Zuffardi, Orsetta, de Leeuw, Nicole, Firth, Helen, Sanlaville, Damien, Clayton-Smith, Jill, Szuhai, Karoly, Vermeesch, Joris Robert, Fiegler, Heike, Rauch, Anita, Van Ravenswaaij, Conny, Patsalis, Philippos C, Devriendt, Koen, Ciccone, Roberto, Speleman, Frank

2007

Overview

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.

• Publisher: Springer International Publishing,Nature Publishing,Nature Publishing Group
• Subject: Bioinformatics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Child / Cytogenetics / Developmental Disabilities - diagnosis / Developmental Disabilities - genetics / Fundamental and applied biological sciences. Psychology / Gene Expression / General aspects. Genetic counseling / Genetics of eukaryotes. Biological and molecular evolution / Genomics - ethics / Genomics - methods / Human Genetics / Humans / Karyotyping - methods / Medical genetics / Medical sciences / Molecular and cellular biology / Nucleic Acid Hybridization - ethics / Nucleic Acid Hybridization - genetics / Nucleic Acid Hybridization - methods / policy / Practice Guidelines as Topic - standards / Prenatal Diagnosis - ethics / Prenatal Diagnosis - methods / Prenatal Diagnosis - standards