Diagnostic yield by supplementing prenatal metaphase karyotyping with MLPA for microdeletion syndromes and subtelomere imbalances

Objective The aim of the study was to retrospectively assess the relevance of using multiplex ligation-dependent probe amplification (MLPA) for detection of selected microdeletion syndromes (22q11, Prader-Wilh/Angelman, Miller-Dieker, Smith-Magenis, Ip-, Williams), the reciprocal microduplication syndromes and imbalance at the subtelomere regions of chromosomes in a routine prenatal setting Method A total of 530 prenatal samples wet e analysed by commercial MLPA kits (SALSA P064. P036 and P069) in addition to rapid aneuploidy testing and G-band karyotyping Results Among the prenatal samples with a normal metaphase karyotype, nine submicroscopic imbalances were detected. seven 22q11 deletions (Velocardiofacial/DiGeorge syndrome), one 15q11 deletion (Prader-Willi syndrome) and one terminal deletion of the short arm of chromosome 4 (Wolf-Hirschhorn syndrome). All imbalances were found in amniocentesis (AC) taken due to fetal structural malformation and/or other ultrasound scan (US) detected abnormality. The diagnostic yield was 4 1% in the subgroup with structural malformation and 1 6% in the subgroup with other US abnormality Conclusion The data set substantiates that additional MLPA analyses for selected microdeletions and subtelomere imbalances ate valuable in routine prenatal diagnostics. when a malformation(s) and/or other abnormalities are detected by US In contrast. the additional MLPA analyses gave no diagnostic yield in case of increased nuchal translucency (NT) Copyright (C) 2010 John Wiley & Sons, Ltd.