31. Maternal chromosome 18 meiosis II nondisjunction mosaic double trisomy rescue inferred from prenatal chromosomal microarray SNP data

SNP microarrays have the ability to detect imbalances in alleles due to cytogenetically invisible mechanisms, such as copy neutral regions of homozygosity. These regions can unmask recessive disease alleles and may also provide evidence of uniparental disomy (UPD) and the potential risk for imprinting disorders. UPD can arise from rescue of an aneuploid cell line, which may indicate the presence of occult aneuploid mosaicism. Here we report the results of SNP microarray performed on uncultured amniocytes of a 19 weeks gestational age fetus carried by a mother of advanced age with history of recurrent miscarriages. The pregnancy was uneventful and there were no abnormalities observed on ultrasound. The microarray showed a distinct allele pattern on chromosome 18 (CHR.18) with segments having seven B allele frequency tracks interrupted by segments having the expected normal three B allele frequency tracks, suggestive of greater than expected allele combinations. FISH to rule out trisomy 18 mosaicism in 200 nuclei was normal. By modeling the expected allele frequency values under different meiotic nondisjunction hypotheses, we determined that the data observed in the microarray is most consistent with a meiosis II nondisjunction event resolved by double trisomy rescue to two biparental cell lines. Further, the rescue events occurred at different times resulting in mixed proportions of the two cell lines. Parental SNP data revealed that the extra CHR.18 alleles were of maternal origin. This data is consistent with the known origins of CHR.18 aneuploidy, which is most often due to maternal meiosis II nondisjunction. The baby was born healthy and FISH on trophoblastic tissue from two different sites revealed two copies of CHR.18. This case highlights the power of SNP microarray to detect and infer rare events such as double trisomy rescue to two biparental cell lines, which allowed the family to be counseled appropriately.