P20.06: The experience with whole‐genome array as a first‐line cytogenetic test in invasive prenatal diagnosis

Abstract

Comparative Genomic Hybridisation (CGH) array represents a molecular cytogenetic method able to detect submicroscopic copy number variants with a high resolution of hundreds of kb. The aim of this study was to assess the contribution array CGH as a first-line cytogenetic method in routine prenatal diagnosis. This was a prospective study. The workflow for prenatal samples was framed as follows. After the invasive procedure, rapid QF-PCR targeted on Trisomy 13, 18 and 21 was performed. In the case of normal QF-PCR results, we carried on with array CGH. The workflow was introduced in January 2015 for chorionic villi sampling (CVS) and in October 2016 for amniocentesis (AMC). SurePrint G3 Unrestricted Human CGH ISCA v2 8x60K Microarray (Agilent, USA) was used on uncultured CVS/AMC samples. The array resolution was set to ≥ 500 kb in fetuses with normal ultrasound findings and to ≥ 300 kb in fetuses with abnormal ultrasound finding with the exception of smaller deletions/duplication hitting causal genes. In total, 2981 invasive procedures (771 CVS, 2210 AMC) were performed since the beginning of the study. QF-PCR detected Trisomy 13, 18 or 21 in 245 cases (201 (26.1%) CVS, 44 (2.0%) AMC). Therefore, array CGH was conducted in the rest 2703 cases (553 CVS, 2150 AMC). Out of these, 2648 cases had normal results and 55 cases (28 (5.1%) CVS, 27 (1.3%) AMC) showed significant pathological findings. The aberrations were of a size more than 10 Mb in 8 cases, whereas in 47 cases (23 (4.2%) CVS, 24 (1.1%) AMC) the aberration size was below 10Mb. These 47 (1.7%) cases would be thus undetected by conventional karyotyping. Typically, the array results were available up to 7 days after the procedure. Array CGH represents a powerful tool which can be used instead conventional karyotyping in the prenatal diagnosis. The advantage is that it detects 1.7% submicroscopic pathologic deletions/duplications which would be undetected using conventional karyotyping and the results are available typically up to 7 days. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.