Belgian MicroArray prenatal (BEMAPRE) database

J. Muys, K. Janssens, O. Vanakker, Catheline Vilain, Guillaume Smits, Bandelier C., Jean-Hubert Caberg, S. Bulk, A. De Leener, Marjan De Rademaeker, Thomy De Ravel, Julie Désir, A. Destrée, Annelies Dheedene, S Gaillez, B Grisart, AC Hellin, S. Janssens, K. Keymolen, Bjoern MentenB. Pichon, M. Ravoet, N. Revencu, S. Rombout, Catherine Staessen, Ann Van Den Bogaert, Kris Van den Bogaert, Bettina Blaumeiser, Y. Jacquemyn, Koenraad Devriendt

Onderzoeksoutput: Meeting abstract (Journal)

Samenvatting

OBJECTIVES: In Belgium, approximately 6% of the pregnant population undergoes an invasive procedure. As of 2013, samples for invasive prenatal diagnosis are analysed by Chromosomal Microarray Analysis (CMA). Despite the existence of publicly available copy number variant (CNV) databases, interpretation of prenatal CNVs remains difficult given the often limited phenotypic information. Concomitantly with the start of CMA in the prenatal setting, a Belgian national Ad Hoc Committee was established to cope with ambiguous situations and to reach consensus based on literature and previous experiences with similar variants. Moreover, Belgian genetic centers agreed on the establishment of a Belgian MicroArray PREnatal (BEMAPRE) database. METHODS: The framework of a national database was developed in consultation with the Belgian centers for Medical Genetics. All prenatal cases in which a pathogenic CNV or a unclassified variant (UV )>400 kb was detected, will be imported. Next, phenotypic data will be added from immediately after delivery. Moreover, children will be reassessed at the age of 2 to 3 years. Based on genotypic and phenotypic data from hundreds of prenatal cases, we will be able to perform meta-analysis. RESULTS: Our reporting policy is largely determined by the classification of the CNVs in 3 categories, i.e. pathogenic, benign and UV. Benign CNVs and non-actionable incidental findings are reported normal after consulting the Ad Hoc Committee. If UVs have intragenic deletions/duplications in a known gene; are mentioned in literature and/or databases; consist of deletions/duplications covering more than 18 genes or comprise an X-linked gene in a XY fetus, the likeliness of pathogenicity is evaluated. In case of strong arguments for pathogenicity, parents are tested. They are reported if parental phenotype is potentially divergent or if de novo. Known pathogenic variants, risk factors with high penetrance or ultrasound anomalies and actionable incidental 31 Prenatal Diagnosis 2015, 35, 27–109 © 2015 John Wiley & Sons, Ltd. findings are reported to the parents. Since the implementation of CMA in Belgium, 7875 arrays were performed. 252 (3.20 %) were reported as having a pathogenic CNV. 8.66% (682 samples) of all arrays revealed monosomy/trisomy occurrence. Data on the relationship between indication for invasive testing, prenatal phenotype and genotype will be provided. CONCLUSIONS: The development of the BEMAPRE databasewhich includes CNV data on all prenatal invasive tests performed in Belgium is of scientific, clinical and societal importance. It will alloweasy communication about ambiguous cases among the Belgian genetic centers, but at the same time, will be made available to other scientists with questions about difficult-to-interpret prenatal CNVs.
Originele taal-2English
Pagina's (van-tot)31
TijdschriftPrenat Diagn
Volume35
Nummer van het tijdschriftS1
StatusPublished - 2015
EvenementISPD 19th International Conference on Prenatal Diagnosis and Therapy - Washington DC, United States
Duur: 12 jul 201515 jul 2015
http://onlinelibrary.wiley.com/doi/10.1002/pd.4617/epdf

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