Ioannis Papoulidis1, Alexandros Sotiriadis2, Elisavet Siomou1, Elena Papageorgiou1, Makarios Eleftheriades3, Vasilios Papadopoulos4, Eirini Oikonomidou5, Sandro Orru6, Emmanouil Manolakos1, Apostolos Athanasiadis7. 1. Access To Genome - ATG P.C., Thessaloniki, Greece. 2. Second Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki, Greece. 3. EMBRYOCARE Fetal Medicine Center, Athens, Greece. 4. Department of Obstetrics and Gynecology, University of Patras Medical School, Patras, Greece. 5. EuroGenetica S.A., Thessaloniki, Greece. 6. Department of Medical Genetics, Cagliari University, Binaghi Hospital, Cagliari, Italy. 7. First Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Abstract
OBJECTIVE: This study aims to evaluate the diagnostic yield of comparative genomic hybridization microarrays (aCGH) and compare it with conventional karyotype analysis of standard >5-Mb resolution. METHOD: A total of 1763 prenatal samples were analyzed by aCGH (CytoChip Focus Constitutional microarrays, BlueGnome, Cambridge). The diagnostic yield of chromosomal abnormalities detected by aCGH was assessed, compared with conventional karyotype analysis. RESULTS: The result was pathogenic/unknown penetrance in 125 cases (7.1%), and a variant of unknown significance (VOUS) was detected in 13 cases (0.7%). Out of the 125 cases with abnormal findings, 110 were also detected by conventional karyotype analysis. The aCGH increment in diagnostic yield was 0.9% (15/1763) and 1.6% when VOUS were included. Stratifying the sample according to indications for prenatal invasive testing, the highest values of diagnostic yield increment were observed for patients positive for second-trimester sonographic markers (1.5%) and for the presence of fetal structural anomalies (1.3%). In contrast, the incremental yield was marginal in patients with fetus with increased nuchal translucency (0.5%). CONCLUSION: The present study indicates that routine implementation of aCGH offers an incremental yield over conventional karyotype analysis, which is also present in cases with 'milder' indications, further supporting its use as a first-tier test.
OBJECTIVE: This study aims to evaluate the diagnostic yield of comparative genomic hybridization microarrays (aCGH) and compare it with conventional karyotype analysis of standard >5-Mb resolution. METHOD: A total of 1763 prenatal samples were analyzed by aCGH (CytoChip Focus Constitutional microarrays, BlueGnome, Cambridge). The diagnostic yield of chromosomal abnormalities detected by aCGH was assessed, compared with conventional karyotype analysis. RESULTS: The result was pathogenic/unknown penetrance in 125 cases (7.1%), and a variant of unknown significance (VOUS) was detected in 13 cases (0.7%). Out of the 125 cases with abnormal findings, 110 were also detected by conventional karyotype analysis. The aCGH increment in diagnostic yield was 0.9% (15/1763) and 1.6% when VOUS were included. Stratifying the sample according to indications for prenatal invasive testing, the highest values of diagnostic yield increment were observed for patients positive for second-trimester sonographic markers (1.5%) and for the presence of fetal structural anomalies (1.3%). In contrast, the incremental yield was marginal in patients with fetus with increased nuchal translucency (0.5%). CONCLUSION: The present study indicates that routine implementation of aCGH offers an incremental yield over conventional karyotype analysis, which is also present in cases with 'milder' indications, further supporting its use as a first-tier test.