The Belgian MicroArray Prenatal (BEMAPRE) database: A systematic nationwide repository of fetal genomic aberrations

Abstract

Objective With the replacement of karyotyping by chromosomal microarray (CMA) in invasive prenatal diagnosis, new challenges have arisen. By building a national database, we standardize the classification and reporting of prenatally detected copy number variants (CNVs) across Belgian genetic centers. This database, which will link genetic and ultrasound findings with postnatal development, forms a unique resource to investigate the pathogenicity of variants of uncertain significance and to refine the phenotypic spectrum of pathogenic and susceptibility CNVs. Methods The Belgian MicroArray Prenatal (BEMAPRE) consortium is a collaboration of all genetic centers in Belgium. We collected data from all invasive prenatal procedures performed between May 2013 and July 2016. Results In this three‐year period, 13 266 prenatal CMAs were performed. By national agreement, a limited number of susceptibility CNVs and no variants of uncertain significance were reported. Added values for using CMA versus conventional karyotyping were 1.8% in the general invasive population and 2.7% in cases with an ultrasound anomaly. Of the reported CNVs, 31.5% would have remained undetected with non‐invasive prenatal test as the first‐tier test. Conclusion The establishment of a national database for prenatal CNV data allows for a uniform reporting policy and the investigation of the prenatal and postnatal genotype–phenotype correlation.

Experience of chromosomal microarray applied in prenatal and postnatal settings in Hong Kong

“…Reporting policy would vary among laboratories and in different country. A recent publication showed that Belgium had a nationwide uniform approach to prenatal chromosome microarray analysis and reporting (Muys et al, ). For instance, the 15q11.2 and the 16p12.1 microdeletions, the 16p13.11 and the distal 22q11.2 microduplications were not reported while the 15q13.3 and the proximal 16p11.2 microdeletions, the distal 16p11.2 and the 22q11.2 microduplications were reported.…”

Prenatally detected copy number variants in a national cohort: A postnatal follow‐up study

“…The proximal (A‐B) 22q11.2 duplication syndrome is the most frequently reported susceptibility CNV in our Belgian prenatal population 3 . It has a Clingen score of 3 and is a susceptibility factor for developmental delay, epilepsy and dysmorphic features and can also cause microcephaly and coronary heart disease 22 .…”

“…This database facilitates data sharing and communication. In a recent study, 3 analysis of the prenatal data gathered over a 3‐year period showed pathogenic variants in 1.9% of cases; 71% of these cases were cryptic. The 22q11.2 deletion syndrome was the most frequently found genomic disorder.…”

“…Following the introduction of chromosomal microarray (CMA) in prenatal invasive diagnosis, difficulties arose concerning the interpretation and reporting of prenatally detected copy number variants (CNVs) to future parents 1‐7 . Although the added value of using CMA over conventional karyotyping for the analysis of invasively obtained prenatal samples is extensively proven, 8‐14 the higher resolution of the test not only increases detection of clinically relevant CNVs, but also reveals a higher number of variants of unknown significance (VOUS), incidental findings or variants with a variable expression or incomplete penetrance (susceptibility variants).…”

“…They agreed to use CMA for all indications for invasive prenatal testing. As previously published, a uniform national protocol on how to interpret and report variants was developed 3,7 (Table S1).…”