Detection of SRY‐positive46,XX male syndrome by the analysis of cell‐free fetal DNA via non‐invasive prenatal testing

Falco, Luigia De; Savarese, Giovanni; Suero, Teresa; Amabile, Sonia; Ruggiero, Raffaella; Savarese, Pasquale; Fico, Antonio

doi:10.1002/ccr3.2389

Cited by 5 publications

(4 citation statements)

References 21 publications

(31 reference statements)

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“…The software uses a counting‐based algorithm to generate the log-likelihood ratio (LLR) scores for chromosomes 13, 18, and 21, as well as NCV_X and NCV_Y scores for sex classification for each sample. LLR thresholds for calling a sample high or low risk were internally validated, and a decision tree was agreed upon for handling failures [ 21 ]. Samples failed when the sequencing coverage was judged insufficient based on the fetal fraction estimate for the sample, as indicated by the Individualized Fetal Fraction Confidence Test (iFACT), which is a quality control parameter of the VeriSeq TM NIPT Solution v1.…”

Section: Methodsmentioning

confidence: 99%

Performance of cell-free DNA sequencing-based non-invasive prenatal testing: experience on 36,456 singleton and multiple pregnancies

Verde

Falco²,

Torella

et al. 2021

BMC Med Genomics

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Background This paper describes the clinical practice and performance of cell-free DNA sequencing-based non-invasive prenatal testing (NIPT) as a screening method for fetal trisomy 21, 18, and 13 (T21, T18, and T13) and sex chromosome aneuploidies (SCA) in a general Italian pregnancy population. Methods The AMES-accredited laboratory offers NIPT in maternal blood as a screening test for fetal T21, T18, T13 and SCA. Samples were sequenced on a NextSeq 550 (Illumina) using the VeriSeq NIPT Solution v1 assay. Results A retrospective analysis was performed on 36,456 consecutive maternal blood samples, including 35,650 singleton pregnancies, 800 twin pregnancies, and 6 triplet pregnancies. Samples were tested between April 2017 and September 2019. The cohort included 46% elevated-risk and 54% low-risk patients. A result indicative of a classic trisomy was found in 356 (1%) of singleton or twin samples: 254 T21, 69 T18, and 33 T13. In addition, 145 results (0.4%) were indicative of a SCA. Of the combined 501 screen-positive cases, 484 had confirmatory diagnostic testing. NIPT results were confirmed in 99.2% (247/249) of T21 cases, 91.2% (62/68) of T18 cases, 84.4% (27/32) of T13 cases, and 86.7% (117/135) of SCA cases. In the 35,955 cases reported as unaffected by a classic trisomy or SCA, no false negative cases were reported. Assuming that false negative results would be reported, the sensitivity of NIPT was 100.00% for T21 (95% Cl 98.47–100.0), T18 (95% Cl 94.17–100.0), and T13 (95% Cl 87.54–100.0). The specificities were 99.99% (95% Cl 99.98–100.0), 99.98% (95% Cl 99.96–100.0), 99.99% (95% Cl 99.97–100.0), and 99.95% (95% Cl 99.92–99.97) for T21, T18, T13, and SCA, respectively. Conclusion This retrospective analysis of a large cohort of consecutive patients who had whole-genome sequencing-based NIPT for classic trisomies and SCA shows excellent detection rates and low false positive rates.

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Section: Methodsmentioning

confidence: 99%

Performance of cell-free DNA sequencing-based non-invasive prenatal testing: experience on 36,456 singleton and multiple pregnancies

Verde

Falco²,

Torella

et al. 2021

BMC Med Genomics

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“…In our case the NIPS analysis reported a sex chromosomes aneuploidy detected as XXX genotype. As previously reported [ 24 ], the evaluation of the “raw data” for this sample and the comparison of the NIPT results to all clinical validated Triple X cases ([ 15 ] and unpublished data) allowed us to suspect the presence of more than three X chromosomes. Chromosomal analysis on amniocytes from the amniotic fluid showed the 49,XXXXX karyotype, confirming our suspicion.…”

Section: Discussionmentioning

confidence: 83%

Non-Invasive Prenatal Screening: The First Report of Pentasomy X Detected by Plasma Cell-Free DNA and Karyotype Analysis

Falco¹,

Suero²,

Savarese³

et al. 2022

Diagnostics

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Pentasomy X is a sex chromosome anomaly caused by the presence of three extra X chromosomes in females (49,XXXXX instead of 46,XX) and is probably due to a nondisjunction during the meiosis. So far, only five cases prenatally diagnosed were described. The main features in 49,XXXXX karyotype include severe intellectual disability with delayed speech development, short stature, facial dysmorphisms, osseous and articular abnormalities, congenital heart malformations, and skeletal and limb abnormalities. Prenatal diagnosis is often difficult due to the lack of a clear echographic sign like nuchal translucency (NT), and mostly cases were postnatally described. We report the first case of a 49,XXXXX female that was detected by non-invasive prenatal screening (NIPS), quantitative fluorescence polymerase chain reaction (QF-PCR) and a fetal karyotype.

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“…The software uses a counting-based algorithm to generate the log-likelihood ratio (LLR) scores for chromosomes 13, 18, and 21, as well as NCV_X and NCV_Y scores for sex classi cation for each sample. LLR thresholds for calling a sample high or low risk were internally validated, and a decision tree was agreed upon for handling failures [21]. Samples failed when the sequencing coverage was judged insu cient based on the foetal fraction estimate for the sample, as indicated by the Individualized Fetal Fraction Con dence Test (iFACT), which is the quality control parameter of the VeriSeq TM NIPT Solution v1.…”

Section: Sample Collection and Processingmentioning

confidence: 99%

Performance of Cell-Free DNA Sequencing-Based Non-invasive Prenatal Testing: Our Experience on 36456 both Singleton and Multiple Pregnancies.

Verde

Falco²,

Torella

et al. 2021

Preprint

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Background: To describe the clinical practice and performance of cell-free DNA sequencing-based noninvasive prenatal testing as a screening method for detecting trisomy 21, 18, and 13 (T21, T18, and T13, respectively), as well as sex chromosome aneuploidy (SCA), in a general Italian pregnancy population.Methods: The AMES-accredited laboratory offers noninvasive prenatal testing in maternal blood as a clinical screening test for foetal T21, T18, T13 and SCA. Samples were sequenced on a NextSeq 550 (Illumina) using the VeriSeq NIPT Solution v1 assay.Results: A retrospective analysis was performed on a cohort of 36456 consecutive maternal blood samples, including 35650 singleton pregnancies, 800 twin pregnancies, and 6 triplet pregnancies, which were tested between April 2017 and September 2019. The cohort included 46% elevated-risk and 54% low-risk patients. Genetic and/or clinical outcomes were available in 36000 cases (98.7%). In the overall cohort, 356 (1%) results were indicative of classic trisomy: 254 T21, 69 T18, and 33 T13. In addition, 145 results (0.4%) were indicative of SCA. Of the combined 501 screen-positive cases, 484 had confirmatory diagnostic testing results available: 99.2% (247/249) of T21 cases, 91.2% (62/68) of T18 cases, 84.4% (27/32) of T13 cases, and 86.7% (117/135) of SCA cases were confirmed. Follow-up data were available for 98.8% of the 35955 cases reported as unaffected by trisomy or SCA. No false negative cases were reported. The sensitivity of NIPT was 100.00% for T21 (95% Cl 98.47-100.0), T18 (95% Cl 94.17-100.0), T13 (95% Cl 87.54-100.0) and SCA (95% Cl 96.62-100.0). The specificities were 99.99% (95% Cl 99.98-100.0), 99.98% (95% Cl 99.96-100.0), 99.99% (95% Cl 99.97-100.0), and 99.95% (95% Cl 99.92-99.97) for T21, T18, T13, and SCA, respectively.Conclusion: This retrospective analysis of a large cohort of consecutive patients who had whole-genome sequencing-based NIPT for classic trisomies and SCA showed excellent detection rates and low false positive rates.

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Detection of SRY‐positive46,XX male syndrome by the analysis of cell‐free fetal DNA via non‐invasive prenatal testing

Cited by 5 publications

References 21 publications

Performance of cell-free DNA sequencing-based non-invasive prenatal testing: experience on 36,456 singleton and multiple pregnancies

Performance of cell-free DNA sequencing-based non-invasive prenatal testing: experience on 36,456 singleton and multiple pregnancies

Non-Invasive Prenatal Screening: The First Report of Pentasomy X Detected by Plasma Cell-Free DNA and Karyotype Analysis

Performance of Cell-Free DNA Sequencing-Based Non-invasive Prenatal Testing: Our Experience on 36456 both Singleton and Multiple Pregnancies.

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Detection of SRY‐positive46,XX male syndrome by the analysis of cell‐free fetal DNA via non‐invasive prenatal testing

Cited by 5 publications

References 21 publications

Performance of cell-free DNA sequencing-based non-invasive prenatal testing: experience on 36,456 singleton and multiple pregnancies

Performance of cell-free DNA sequencing-based non-invasive prenatal testing: experience on 36,456 singleton and multiple pregnancies

Non-Invasive Prenatal Screening: The First Report of Pentasomy X Detected by Plasma Cell-Free DNA and Karyotype Analysis

Performance of Cell-Free DNA Sequencing-Based Non-invasive Prenatal Testing: Our Experience on&nbsp;36456 both Singleton and Multiple Pregnancies.

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Performance of Cell-Free DNA Sequencing-Based Non-invasive Prenatal Testing: Our Experience on 36456 both Singleton and Multiple Pregnancies.