On the road to replacing invasive testing with cell-based NIPT: Five clinical cases with aneuploidies, microduplication, unbalanced structural rearrangement, or mosaicism

TY - JOUR

T1 - On the road to replacing invasive testing with cell-based NIPT

T2 - Five clinical cases with aneuploidies, microduplication, unbalanced structural rearrangement, or mosaicism

AU - Vestergaard, Else Marie

AU - Singh, Ripudaman

AU - Schelde, Palle

AU - Hatt, Lotte

AU - Ravn, Katarina

AU - Christensen, Rikke

AU - Lildballe, Dorte Launholt

AU - Petersen, Olav Bjørn

AU - Uldbjerg, Niels

AU - Vogel, Ida

N1 - © 2017 John Wiley & Sons, Ltd.

PY - 2017/11

Y1 - 2017/11

N2 - OBJECTIVE: Trophoblastic fetal cells harvested from maternal blood have the capacity to be used for copy number analyses in a cell-based non-invasive prenatal test (cbNIPT). Potentially, this will result in increased resolution for detection of subchromosomal aberrations due to high quality DNA not intermixed with maternal DNA. We present 5 selected clinical cases from first trimester pregnancies where cbNIPT was used to demonstrate a wide range of clinically relevant aberrations.METHOD: Blood samples were collected from high risk pregnancies in gestational week 12 + 1 to 12 + 5. Fetal trophoblast cells were enriched and stained using fetal cell specific antibodies. The enriched cell fraction was scanned, and fetal cells were picked using a capillary-based cell picking instrument. Subsequently, whole genome amplification (WGA) was performed on fetal cells, and the DNA was analyzed blindly by array comparative genomic hybridization (aCGH).RESULTS: We present 5 cases where non-invasive cell-based prenatal test results are compared with aCGH results on chorionic villus samples (CVS), demonstrating aneuploidies including mosaicism, unbalanced translocations, subchromosomal deletions, or duplications.CONCLUSION: Aneuploidy and subchromosomal aberrations can be detected using fetal cells harvested from maternal blood. The method has the future potential of being offered as a cell-based NIPT with large high genomic resolution.

AB - OBJECTIVE: Trophoblastic fetal cells harvested from maternal blood have the capacity to be used for copy number analyses in a cell-based non-invasive prenatal test (cbNIPT). Potentially, this will result in increased resolution for detection of subchromosomal aberrations due to high quality DNA not intermixed with maternal DNA. We present 5 selected clinical cases from first trimester pregnancies where cbNIPT was used to demonstrate a wide range of clinically relevant aberrations.METHOD: Blood samples were collected from high risk pregnancies in gestational week 12 + 1 to 12 + 5. Fetal trophoblast cells were enriched and stained using fetal cell specific antibodies. The enriched cell fraction was scanned, and fetal cells were picked using a capillary-based cell picking instrument. Subsequently, whole genome amplification (WGA) was performed on fetal cells, and the DNA was analyzed blindly by array comparative genomic hybridization (aCGH).RESULTS: We present 5 cases where non-invasive cell-based prenatal test results are compared with aCGH results on chorionic villus samples (CVS), demonstrating aneuploidies including mosaicism, unbalanced translocations, subchromosomal deletions, or duplications.CONCLUSION: Aneuploidy and subchromosomal aberrations can be detected using fetal cells harvested from maternal blood. The method has the future potential of being offered as a cell-based NIPT with large high genomic resolution.

KW - Chromosome Aberrations

KW - Female

KW - Humans

KW - Maternal Serum Screening Tests

KW - Pregnancy

U2 - 10.1002/pd.5150

DO - 10.1002/pd.5150

M3 - Journal article

C2 - 28881392

SN - 0197-3851

VL - 37

SP - 1120

EP - 1124

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

IS - 11

ER -