13. Revisiting centromeric polymorphisms: Implications for POC and prenatal interphase FISH studies

      Interphase FISH is a routinely used rapid method to detect or confirm common prenatal aneuploidies (13, 18, 21, X, Y). Rare aneuploidies are typically observed in products of conception (POC) samples and now more recently in NIPT samples that undergo whole genome assessment. As such, FISH with expanded aneuploidy panels are being used more frequently in prenatal or POC samples to detect or confirm rare autosomal aneuploidies. We report on cases where polymorphisms in the centromeric regions have affected the interpretation of interphase FISH results. Discrepant FISH results were seen in three unrelated pregnancies involving testing of POCs. Aneuploidy interphase FISH indicated monosomy 15 in POC-1, however karyotype and metaphase FISH studies revealed a normal female karyotype with only one chromosome 15 centromere that showed a positive signal for the chr15 centromeric probe (D15Z1). Aneuploidy interphase FISH indicated trisomy 15 for POC-2, however karyotype and metaphase FISH studies revealed a normal male karyotype with a third hybridization signal for the D15Z1 probe located in the centromeric region of one of the chr13 homologues. Aneuploidy interphase FISH testing on POC-3 showed monosomy 16. However, follow-up interphase FISH with a locus-specific probe on chromosome 16q22 (CBFB) indicated disomy for chr16. Alpha satellite polymorphisms, while rare, are well documented in the literature. Strategies to counteract incorrect interpretation resulting from these polymorphisms include the concurrent use of a second locus-specific probe for the same chromosome. These results highlight the possibility of encountering alpha satellite polymorphisms in clinical interphase FISH studies with the potential of reporting inaccurate fetal aneuploidy status if follow-up karyotype (with metaphase FISH) or CMA studies are not performed.
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