Rare autosomal trisomies: Important and not so rare

Scott, Fergus; Bonifacio, Michael; Sandow, Rhiannon; Ellis, Katie; Smet, Maria‐Elisabeth; McLennan, Andrew

doi:10.1002/pd.5325

Cited by 69 publications

(69 citation statements)

References 18 publications

(34 reference statements)

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“…One of the main study limitations was that this was a selected set of pregnancy samples and thus may not be truly representative of a larger general pregnancy population. Other recent publications have looked at genome-wide NIPT in patient populations of at least 10,000 patients [5,6,34,43], with a few publications reporting results from populations of over 50,000 patients [28,44,45]. However, the observed assay failure rate and FF distribution in our study population were consistent with those observed in the referral population, suggesting the data is representative.…”

Section: Discussionsupporting

confidence: 82%

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Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies

Kleinfinger

Lohmann

Luscan

et al. 2020

JCM

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Atypical fetal chromosomal anomalies are more frequent than previously recognized and can affect fetal development. We propose a screening strategy for a genome-wide non-invasive prenatal test (NIPT) to detect these atypical chromosomal anomalies (ACAs). Two sample cohorts were tested. Assay performances were determined using Cohort A, which consisted of 192 biobanked plasma samples—42 with ACAs, and 150 without. The rate of additional invasive diagnostic procedures was determined using Cohort B, which consisted of 3097 pregnant women referred for routine NIPT. Of the 192 samples in Cohort A, there were four initial test failures and six discordant calls; overall sensitivity was 88.1% (37/42; CI 75.00–94.81) and specificity was 99.3% (145/146; CI 96.22–99.88). In Cohort B, there were 90 first-pass failures (2.9%). The rate of positive results indicating an anomaly was 1.2% (36/3007) and 0.57% (17/3007) when limited to significant unbalanced chromosomal anomalies and trisomies 8, 9, 12, 14, 15, 16, and 22. These results show that genome-wide NIPT can screen for ACAs with an acceptable sensitivity and a small increase in invasive testing, particularly for women with increased risk following maternal serum screening and by limiting screening to structural anomalies and the most clinically meaningful trisomies.

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Section: Discussionsupporting

confidence: 82%

“…In France, these ACAs account for 12.25% of all prenatal unbalanced chromosomal abnormalities and 2.5% of all prenatal karyotypes [31]. These ACAs have been shown to be associated with a poor prognosis, including miscarriage, intrauterine fetal death, intellectual development disorders, and malformative syndromes [29,[32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies

Kleinfinger

Lohmann

Luscan

et al. 2020

JCM

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show abstract

“…This was then expanded to include optional testing for fetal sex and sex chromosome aneuploidies [12,13], and later to include the option of screening for common microdeletions [14,15], rare autosomal aneuploidies, and partial deletions and duplications [16][17][18]. The additional fetal anomalies that are captured following genome-wide testing can impact patient management as they are often associated with serious pregnancy complications [16,19]. The ability of commercially available NIPT assays to detect additional fetal anomalies is dependent on the technology used by the assay.…”

Section: Introductionmentioning

confidence: 99%

Analysis of cell-free DNA in a consecutive series of 13,607 routine cases for the detection of fetal chromosomal aneuploidies in a single center in Germany

Borth

Teubert

Glaubitz

et al. 2020

Arch Gynecol Obstet

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Purpose Noninvasive prenatal testing (NIPT) is a highly sensitive and specific method for detection of fetal chromosomal aneuploidies from maternal plasma. The objective of this study was to determine the performance of a new paired-end sequencing-based NIPT assay in 13,607 pregnancies from a single center in Germany. Methods Samples from 13,607 pregnant women who previously underwent NIPT were analyzed using VeriSeq NIPT Solution v2 assay for presence of common fetal trisomies and monosomy X. Follow-up to determine clinical truth was carried out. Results Of the 13,607 cases, 13,509 received a NIPT call resulting in a low study failure rate of 0.72%. There were 188 (1.4%) high-risk calls: 117 trisomy 21, 34 trisomy 18, 23 trisomy 13, one trisomy 21 + 13, and 13 monosomy X. High sensitivities and specificities of ≥ 98.89% were reported for all four aneuploidy conditions. Of the high-risk cases, clinical follow-up data were available for 77.1% (145/188). Clinical follow-up of high-risk calls revealed an overall positive predictive value of 84.8% (potential range 65.4–88.3%). NIPT results were provided for samples across a range of fetal fractions, down to 2% fetal fraction. Conclusion The VeriSeq NIPT Solution v2 assay detected fetal chromosomal aneuploidies across a range of fetal fractions with high sensitivities and specificities observed based on known clinical outcomes, a high overall PPV, and a low failure rate.

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“…NIPT can evaluate chromosomes other than 13, 18, 21, X and Y. Rare autosomal trisomy (RAT) can have sometimes adverse effects on pregnancy outcomes [10,11]. The most common RAT detected in NIPT involved chromosome 7 and 16 [12].…”

Section: Introductionmentioning

confidence: 99%

Prenatal diagnosis of mosaic trisomy 2 and literature review

et al. 2020

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Background: We presented two cases of mosaic trisomy 2 with high risk of maternal serum screening and noninvasive prenatal testing (NIPT). The invasive amniocentesis was performed and genetic tests including karyotype, single nucleotide polymorphism array(SNP-array), interphase fluorescence in situ hybridization (FISH) were employed to detect the chromosomal abnormality. Results: Cytogentic analysis of the case 1 and 2 showed a mosaic karyotype consisting of two cell lines (mos 47,XY, +2[8]/46,XY[19] and mos 47,XX,+2[7]/46,XX[28], respectively). SNP-array using DNA extracted from uncultured amniotic fluid cells revealed a result of arr[GRCh38](2)x2~3, which indicated that chromosome 2 may be trisomy of mosaicism in both two cases. The results of interphases FISH confirmation test showed that three red signals of the CEP 2 specific probe in 14%(14/100) and 12%(12/100) of the two cases' cells, respectively, which indicated a mosaicism for trisomy 2 in the uncultured amniocytes. Fetal ultrasound of case 1 suggested that the long bone is smaller than the gestational age, while the case 2 showed that the biparietal diameter (BPD), head circumference (HC) and femur length (FL) were smaller than gestational age along with abnormal cardiac structure. Conclusions: We presented two cases with mosaic trisomy 2 and performed confirmatory genetic testing using cultured and uncultured amniocytes. When maternal serum screening and NIPT suggesting high risk, genetic counselor should be alert for increasing possibility of chromosomal anomalies if combined with abnormal ultrasound findings.

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Rare autosomal trisomies: Important and not so rare

Cited by 69 publications

References 18 publications

Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies

Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies

Analysis of cell-free DNA in a consecutive series of 13,607 routine cases for the detection of fetal chromosomal aneuploidies in a single center in Germany

Prenatal diagnosis of mosaic trisomy 2 and literature review

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