Prenatal detection by subtelomeric FISH and MLPA of unbalanced meiotic recombinants resulting from parental pericentric inversions

ObjectivePericentric inversion carriers are predisposed to produce unbalanced gametes that result in conceptuses having either a partial trisomy for one distal segment and a partial monosomy for the other or vice versa. Larger inversions result in smaller unbalanced distal segments and a higher likelihood of a viable fetus. In these cases the structure of the recombinant chromosome is similar to the original balanced inverted or normal ones despite the (unbalanced) genetic content. Such cases may not be detected prenatally by conventional cytogenetic analysis.MethodsIn all prenatal samples from the pericentric inversion carriers we applied subtelomeric FISH probes specific for the chromosome involved in order to detect parental meiotic recombinants resulting from a single cross-over event. Confirmatory MLPA was also applied in unbalanced fetuses.ResultsThe occurrence of a duplication deficiency unbalance from pericentric inversion carriers was successfully detected in all three fetuses by FISH. MLPA assays applied in two cases confirmed these results.ConclusionsThe application of commercial FISH subtelomeric probes is a reliable method that could be routinely applied for the detection of single cross-over meiotic recombinants. MLPA is a sound alternative technique.