No abstract

Objective/Material and Method: Cryptic chromosomal imbalances contribute significantly to the etiology of multiple congenital anomalies with or without mental retardation (MCA/MR). Current approaches in prenatal diagnosis include targeted high resolution analyses by MLPA and some microarray platforms or a genomewide screening at maximal resolution using oligonucleotide or SNP arrays. The major disadvantages of the latter approach are cost and the inadvertent detection of copy number variation of unknown clinical significance. In this prospective work, fetal DNA samples from 66 fetuses who had pathological antenatal ultrasonography findings with normal karyotype and Multiprobe T-FISH results were tested using commercially available targeted MLPA probe-sets to compare the efficacy and the impact of MLPA testing at prenatal setting. Results: Three submicroscopic deletions (3.66; 4.5%) were detected in the cohort. Two of them were de novo deletions, 18ptel and 7q11.23. The third finding was a 75 kb duplication at 18q, which was maternally inherited and probably a benign copy number variation unrelated to the pathological ultarsonography findings. Conclusion: The observed detection rate by MLPA testing can be considered within the expected range. Furthermore, benign copy number variation was identified with the targeted diagnostic approach as an unexpected finding. This study shows that MLPA is a practical and cost-effective technique to investigate submicroscobic chromosomal aberrations in fetuses.