The BElgian PREnatal MicroArray consortium: towards relating prenatally detected CNVs, prenatal phenotype and postnatal clinical data.
Joke Muys1, Bettina Blaumeiser2, Yves Jacquemyn3, Koenraad Devriendt4, Sandra Janssens5, Kathelijn Keymolen6, Sonia Rombout7, Jean-Stéphane Gatot8, Julie Desir7, Yves Sznajer9, Marije Meuwissen10, Joris Vermeesch4, Bjorn Menten5, Annelies Fieuw11, Benoit Parmentier12, Saskia Bulk13, Bruno Pichon14, Claude Bandelier9, Erik Fransen15, Kris Van Den Bogaert4, Annelies Dheedene5, Marjan De Rademaeker6, Anne Destree7, Winnie Courtens, Anne Deleener, Nathalie Brison, Olivier Vanakker5, Ann Van Den Bogaert6, Mauricette Jamar, patrizia chiarappa, Damien Lederer12, - The Belgian Microarray Prenatal Consortium (BEMAPRE), Katrien Janssens
1University Hospital Antwerp, Edegem, Belgium, Belgium
2Center for Medical genetics, Universiteit Antwerpen, Antwerp, Belgium
3University Hospital Antwerp, Edegem, Belgium
4Center for Medical genetics, Katholieke Universiteit Leuven, Leuven, Belgium
5Center for Medical genetics, Universiteit Gent, Ghent, Belgium
6Center for Medical genetics, Vrije Universiteit Brussel, Brussels, Belgium
7Center for Medical genetics, IPG, Charleroi Gosselies, Charleroi Gosselies, Belgium
8Center for Medical Genetics, Université de Liège, Belgium, Liège, Belgium
9Center for Medical genetics, Université Catholique de Louvain, Louvain, Belgium
10Center for Medical Genetics, Universiteit Antwerpen, Edegem, Belgium
11Center for Medical Genetics, Vrije Universiteit Brussel, Brussel, Belgium
12Center for Medical Genetics, IPG, Charleroi Gosselies, Gosselies, Belgium
13Center for Medical genetics, Université de Liège, Liège, Belgium
14Center for Medical genetics, Université Libre de Bruxelles, Brussels, Belgium
15University of Antwerp, Edegem, Belgium Center for Medical Genetics, Université Catholique Louvain, Sint Lambrechts Woluwe, Belgium Center for Human Genetics, University Hospital Leuven, Leuven, Belgium Center for Medical Genetics, Université Catholique de Louvain, Brussel, Belgium Belgian Society for Human Genetics (http://www.beshg.be), Edegem, Belgium Center for Medical genetics, Universiteit Antwerpen, Antwerpen, Belgium
Objectives
The uncertainty concerning the significance and clinical implications of some prenatally identified CNVs detected using microarray (CMA) underscores the urgency and importance of the development of an appropriate database relating prenatal genetic and ultrasound findings with postnatal clinical and neurodevelopmental data. The unique BElgian PREnatal MicroArray (BEMAPRE) collection allows us to identify the most frequent pathogenic CNVs, susceptibility CNVs and VOUS in the Belgian prenatal population and to calculate added values for the use of CMA versus karyotyping. Moreover, this database is the basis for longitudinal studies on the developmental effect of CNVs.
Methods
The BEMAPRE consortium is a collaboration of all eight genetic centers in Belgium. We collected data from invasive prenatal procedures performed between May 2013 and July 2016. In this period, 13266 prenatal CMAs were performed in Belgium. For each invasive prenatal procedure, centers provided the indication for the invasive test and the obtained CMA results. Descriptive statistics were used to describe population, patient and CNV characteristics. SPSS 24 was applied to analyze data. Frequency tables describing the association between indication and mutation type were visualized using correspondence analysis.
Results
Invasive prenatal procedures were performed in on average 3.6% of pregnancies per year. There was a gradual decline of 61.3% since 2007. Added values for using CMA versus conventional karyotyping were 1.8% in the general invasive population; 2.7% in cases with an ultrasound anomaly. The 22q11.2 duplication and the 15q11.2 duplication are respectively the most frequently reported and unreported susceptibility CNVs. Correspondence analysis did not detect an association between indication of the test and finding a susceptibility CNV. Up to 22.1% of reported diagnoses would have remained undetected with ‘genome-wide NIPT’ as the first-tier test. Postnatal follow-up is currently ongoing.
Conclusions
Our prenatal strategy is unique, as Belgium is currently the only country with a nationwide uniform approach of prenatal CMA analysis, reporting and communal CNV data storage. Only a limited number of susceptibility CNVs and none of the VOUS are reported. No association between the indication of the test and finding a susceptibility CNV was detected. With the implementation of NIPT, invasive prenatal testing increasingly becomes restricted to pregnancies with ultrasound anomalies and those with a familial genetic disorder. Subchromosomal pathogenic CNVs will be missed.
