TY - JOUR
T1 - Origin and clinical relevance of chromosomal aberrations other than the common trisomies detected by genome-wide NIPS: results of the TRIDENT study
AU - Van Opstal, Diane
AU - van Maarle, Merel C.
AU - Lichtenbelt, Klaske
AU - Weiss, Marjan M.
AU - Schuring-Blom, Heleen
AU - Bhola, Shama L.
AU - Hoffer, Mariette J. V.
AU - Huijsdens-van Amsterdam, Karin
AU - Macville, Merryn V.
AU - Kooper, Angelique J. A.
AU - Faas, Brigitte H. W.
AU - Govaerts, Lutgarde
AU - Tan-Sindhunata, Gita M.
AU - den Hollander, Nicolette
AU - Feenstra, Ilse
AU - Galjaard, Robert-Jan H.
AU - Oepkes, Dick
AU - Ghesquiere, Stijn
AU - Brouwer, Rutger W. W.
AU - Beulen, Lean
AU - Bollen, Sander
AU - Elferink, Martin G.
AU - Straver, Roy
AU - Henneman, Lidewij
AU - Page-Christiaens, Godelieve C.
AU - Sistermans, Erik A.
AU - Dutch NIPT Consortium
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Purpose: Noninvasive prenatal screening (NIPS) using cell-free DNA in maternal blood is highly sensitive for detecting fetal trisomies 21, 18, and 13. Using a genome-wide approach, other chromosome anomalies can also be detected. We report on the origin, frequency, and clinical significance of these other chromosome aberrations found in pregnancies at risk for trisomy 21, 18, or 13. Methods: Whole-genome shallow massively parallel sequencing was used and all autosomes were analyzed. Results: In 78 of 2,527 cases (3.1%) NIPS was indicative of trisomy 21, 18, or 13, and in 41 (1.6%) of other chromosome aberrations. The latter were of fetal (n = 10), placental (n = 22), maternal (n = 1) or unknown (n = 7). One case lacked cytogenetic follow-up. Nine of the 10 fetal cases were associated with an abnormal phenotype. Thirteen of the 22 (59%) placental aberrations were associated with fetal congenital anomalies and/or poor fetal growth (<p10), which was severe (<p2.3) in six cases. Conclusion: Genome-wide NIPS in pregnancies at risk for trisomy 21, 18, or 13, reveals a chromosomal aberration other than trisomy 21, 18 or 13 in about one-third of the abnormal cases. The majority involves a fetal or placental chromosome aberration with clinical relevance for pregnancy management.
AB - Purpose: Noninvasive prenatal screening (NIPS) using cell-free DNA in maternal blood is highly sensitive for detecting fetal trisomies 21, 18, and 13. Using a genome-wide approach, other chromosome anomalies can also be detected. We report on the origin, frequency, and clinical significance of these other chromosome aberrations found in pregnancies at risk for trisomy 21, 18, or 13. Methods: Whole-genome shallow massively parallel sequencing was used and all autosomes were analyzed. Results: In 78 of 2,527 cases (3.1%) NIPS was indicative of trisomy 21, 18, or 13, and in 41 (1.6%) of other chromosome aberrations. The latter were of fetal (n = 10), placental (n = 22), maternal (n = 1) or unknown (n = 7). One case lacked cytogenetic follow-up. Nine of the 10 fetal cases were associated with an abnormal phenotype. Thirteen of the 22 (59%) placental aberrations were associated with fetal congenital anomalies and/or poor fetal growth (<p10), which was severe (<p2.3) in six cases. Conclusion: Genome-wide NIPS in pregnancies at risk for trisomy 21, 18, or 13, reveals a chromosomal aberration other than trisomy 21, 18 or 13 in about one-third of the abnormal cases. The majority involves a fetal or placental chromosome aberration with clinical relevance for pregnancy management.
KW - confined placental mosaicism
KW - genome-wide NIPS
KW - noninvasive testing
KW - prenatal screening
KW - trisomy 21
KW - CONFINED PLACENTAL MOSAICISM
KW - CELL-FREE DNA
KW - PRENATAL-DIAGNOSIS
KW - FOLLOW-UP
KW - MATERNAL MALIGNANCIES
KW - DUTCH LABORATORIES
KW - TERM PLACENTAE
KW - CVS MOSAICISM
KW - FETAL DNA
KW - ANEUPLOIDIES
KW - CONFIRMATION
KW - ANEUPLOIDY
KW - ASSOCIATION
KW - Chromosome Disorders/diagnosis
KW - Trisomy
KW - Humans
KW - DNA Copy Number Variations
KW - Female
KW - Placenta/metabolism
KW - Genomics/methods
KW - Whole Genome Sequencing
KW - Pregnancy
KW - Prenatal Diagnosis/methods
KW - Genetic Testing/methods
KW - Chromosome Aberrations
KW - Pregnancy Outcome
U2 - 10.1038/gim.2017.132
DO - 10.1038/gim.2017.132
M3 - Article
C2 - 29121006
SN - 1098-3600
VL - 20
SP - 480
EP - 485
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 5
ER -