Background Conventional cytogenetic analysis using G-band karyotyping has been the method of choice for prenatal diagnosis, accurately detecting chromosomal abnormalities larger than 5 Mb. However, the method is inefficient for detecting the submicroscopic deletions and duplications that are associated with malformations and mental retardation. This study evaluated the results of the multiplex ligation-dependent probe amplification (MLPA) P245 assay used for prenatal diagnosis in cases with unusual ultrasonographic findings or specifically where parents wanted to be tested. The objective was to compare the results from MLPA with those from conventional cytogenetic testing in order to determine their concordance and the additional diagnostic yield of MLPA over G-band karyotyping. Results Of the 7522 prenatal cases analyzed, 124 were found to have genomic imbalances (1.6%). Of those 124 cases, 41 had gene loss (33.6%), and 83 had gene gain (66.4%). Most of the cases with genomic imbalances (64.5%) showed no abnormal karyotype. In particular, all cases with a 4p16.3 deletion (Wolf-Hirschhorn syndrome) showed an abnormal karyotype, whereas all of those with a 22q11–13 deletion showed a normal karyotype. In most of the cases with pathogenic deletions, the indication for invasive prenatal testing was an increase in the nuchal translucency (NT) alone (51.2%). Other indications observed in the remaining cases were abnormal serum screening markers (14.6%), other ultrasonographic findings (9.8%), pregnancy through in vitro fertilization and fertility assistance (9.8%), and advanced maternal age(2.4%). Conclusions These results show that for fetuses with an enlarged NT or abnormal ultrasonographic findings and normal conventional karyotype, additional genetic investigation like molecular testing would be for identifying the microscopic genomic aberrations (microdeletions, microduplications) responsible for syndromic associations including structural anomalies and mental retardation.

Purpose: To evaluate the additive value of prenatal chromosomal microarray analysis (CMA) in assessing increased nuchal translucency (NT) (≥3.5 mm) with normal karyotype and the possibility of detecting clinically significant genomic imbalance, based on specific indications. Materials and Methods: Invasive samples from 494 pregnancies with NT ≥3.5 mm, obtained from the Research Center of Fertility & Genetics of Hamchoon Women's Clinic between January 2019 and February 2020, were included in this study and CMA was performed in addition to a standard karyotype. Results: In total, 494 cases were subjected to both karyotype and CMA analyses. Among these, 199 cases of aneuploidy were excluded. CMA was performed on the remaining 295 cases (59.7%), which showed normal (231/295, 78.3%) or non-significant copy number variation (CNV), such as benign CNV or variants of uncertain clinical significance likely benign (53/295, 18.0%). Clinically significant CNVs were detected in 11 cases (11/295, 3.7%). Conclusion: Prenatal CMA resulted in a 3% to 4% higher CNV diagnosis rate in fetuses exhibiting increased NT (≥3.5 mm) without other ultrasound detected anomalies and normal karyotype. Therefore, we suggest using high resolution, non-targeting CMA to provide valuable additional information for prenatal diagnosis. Further, we recommend that a genetics specialist should be consulted to interpret the information appropriately and provide counseling and follow-up services after prenatal CMA.