Abstract
(Abstracted from Lancet 2019;393:747–757) Fetal structural anomalies, detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs), and pathogenic sequence variants in developmental genes. Conventional prenatal cytogenetic analysis was historically the first-line method to investigate these anomalies, but chromosomal microarray analysis has been adopted more recently, as this test is able to detect smaller, but significant, CNVs.
Highlights
3% of pregnancies will show a fetal structural anomaly in a sonogram, which can range from a single minor defect to severe multisystem anomalies that are fatal.[1]
The cohort was recruited between Oct 22, 2014, and June 29, 2017, and clinical data were collected until March 31, 2018
To estimate the number of eligible cases that were excluded from whole-exome sequencing (WES), a retrospective review of 564 eligible fetuses revealed that 134 (23·8%) samples were not sent for WES because of an abnormal quantitative fluorescence-PCR analysis (n=97) or chromosomal microarray (n=37) finding
Summary
3% of pregnancies will show a fetal structural anomaly in a sonogram, which can range from a single minor defect to severe multisystem anomalies that are fatal.[1] Genetic investigations are important in the evaluation and clinical triage of fetal structural anomalies. For more than 30 years, conventional prenatal cytogenetic analysis was the first-line method to investigate these anomalies but, within the last 10 years, chromosomal microarray analysis has been increasingly adopted to detect submicroscopic pathogenic copy number varia tions (CNVs) in prenatal diagnoses.[2,3] The addition of chromosomal microarray testing to karyotyping increases the frequency of detection of chromosomal abnormalities by 3–5%.2–4. There is increasing interest in genome-wide sequencing strategies to investigate prenatally detected congenital abnormalities. Prenatal whole-genome sequencing (WGS) has previously been described,[5] but whole-exome sequencing (WES) and targeted gene panels have received more interest because of their lower cost, the lower amounts of fetal DNA required, the possibility of com paratively more rapid turnaround, and greater sequencing depth.[6,7,8,9,10,11,12,13] We previously used WES in 29 fetal-parental trios
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