Abstract
ObjectiveThe aim of this study was to validate the results of two Emanuel syndromes detected by non-invasive prenatal screening (NIPS) screening using invasive methods, providing clinical performance of NIPS on chromosome microduplication detection.MethodsNIPS was performed to diagnose the Emanuel syndrome. Amniocentesis or cordocentesis was performed to confirm the positive screening result of Emanuel syndrome cases. Fetal sample was detected by karyotyping, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism array (SNP Array). Parental karyotyping and FISH were also carried out.ResultsTwo cases with chromosomal abnormalities of 11q23.3q25 and 22q11.1q11.21 were found by NIPS. Chromosomal karyotyping showed that the two fetuses each have a small supernumerary marker chromosome (sSMC), SNP Array further demonstrated double duplications approximately 18 Mb in 11q23.3q25 and 3 Mb in 22q11.1q11.21. FISH confirmed that the small supernumerary marker chromosome (sSMC) was ish der(22)t(11;22) (TUPLE1+, ARSA-). Ultrasound scan and MRI showed some structure malformations in two fetuses. The two mothers were found to be a balanced carrier: 46,XX, t(11;22)(q23.3;q11.2).ConclusionNIPS could effectively identify Emanuel syndrome, which may indicate risks of a parent being a balanced rearrangement carrier. The followed confirmation test for positive sample is necessary and ensures the accuracy of the diagnosis.
Highlights
In the past years, with the rapid development of nextgeneration sequencing (NGS) and the discovery of cellfree fetal DNA, non-invasive prenatal screening (NIPS) has brought profound changes to detect common autosomal aneuploidies and genetic conditions early in pregnancy using a maternal plasma test [1].The availability of NIPS is obvious, avoiding the risk of miscarriage caused by invasive prenatal diagnostic methods
The correct detection of duplication region by NIPS was verified by three different molecular methods, indicating that non-invasive screening can be applied to screen for Emanuel syndrome (ES). This is a proof of concept study with potential clinical implementation in NIPS
We report here two fetuses with ES determined by NIPS and confirmed by invasive diagnosis
Summary
With the rapid development of nextgeneration sequencing (NGS) and the discovery of cellfree fetal DNA (cfDNA), non-invasive prenatal screening (NIPS) has brought profound changes to detect common autosomal aneuploidies and genetic conditions early in pregnancy using a maternal plasma test [1].The availability of NIPS is obvious, avoiding the risk of miscarriage caused by invasive prenatal diagnostic methods. The clinical validity and utility of NIPS for common autosomal aneuploidies (trisomies 13, 18, and 21) have been endorsed by various clinical guidelines for high risk pregnancies [2]. In a recent meta-analysis in which the results of a large number of studies were pooled, NIPS (2020) 13:9 was found to have a detection rate(DR) of 99.7% for trisomy 21, and a false-positive rate (FPR) of 0.04%.For trisomy 18, the reported figures were 97.9% (DR) and 0.04% (FPR). There is no evidence to support that NIPS can detect ES, which is a double-segment chromosome duplication of 11q23.3q25 and 22q11.1q11.21
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