Objective: To evaluate the usefulness of subtelomeric multiplex ligation-dependent probe amplification (MLPA) in both the detection of subtelomeric rearrangements in fetuses with ultrasound abnormalities and normal karyotype, and the characterization of cytogenetically detectable rearrangements.
Method: We studied by subtelomeric MLPA 229 pregnancies with ultrasound findings and normal karyotype (Group 1) and five pregnancies with a cytogenetically visible but not microscopically characterizable rearrangement (Group 2). The detected imbalances were confirmed by fluorescence in situ hybridization (FISH) and parents were also studied.
Results: In Group 1, two clinically relevant subtelomeric imbalances (14qter deletion and 20pter deletion) and one subtelomeric imbalance of uncertain significance (X/Ypter duplication) were diagnosed, showing a detection rate of cryptic subtelomeric imbalances in these pregnancies of 1.3%. However, only 14qter deletion seems to be clearly associated with the observed prenatal findings. In Group 2, MLPA contributed to the precise description of the chromosome abnormalities.
Conclusion: The low detection rate of subtelomeric imbalances and the poor genotype-phenotype correlations in pregnancies with ultrasound abnormalities and normal karyotype suggest that subtelomeric MLPA is not a crucial tool in the prenatal diagnosis of these cases. However, our work provides evidence that MLPA is very useful for the characterization of unbalanced karyotypes. Copyright © 2010 John Wiley & Sons, Ltd.