Clinical experience with multiplex ligation-dependent probe amplification for microdeletion syndromes in prenatal diagnosis: 7522 pregnant Korean women

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.