Reducing false positive rate of fetal monosomy X in non‐invasive prenatal testing using a combined algorithm to detect maternal mosaic monosomy X

Phan, Minh-Duy; Vo, Binh Thanh; Nguyen, Thong Van; Tran, Nam Quang; Trinh, Huong N T; Nguyen, Tho T Q; Nguyen, Nguyen Hong; Tran, Truong T; Tran, Uyen Vu; Dao, Thuy Thi-Thanh; Pham, Anh Huynh Tram; Tran, Tam H; Truong, Kiet Dinh; Hoang, Tuyet Thi Diem; Thanh-Thuy, T; Nguyen, Hoai-Nghia; Giang, Hoa

doi:10.1002/pd.5430

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…Few studies have focused on the reasons for discordant NIPS results for SCAs. To date, only a few cases of false‐positive NIPS for SCAs have been described in previous studies . Our study represents a large‐scale clinical study assessing the impact of maternal sex chromosome abnormalities on NIPS SCAs.…”

Section: Discussionmentioning

confidence: 96%

High false‐positive non‐invasive prenatal screening results for sex chromosome abnormalities: Are maternal factors the culprit?

et al. 2019

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Objective To explore the impact of maternal sex chromosome aneuploidies (SCAs) and copy number variation (CNV) on false‐positive results of non‐invasive prenatal screening (NIPS) for predicting foetal SCAs. Methods In total, 22 844 pregnant women were recruited to undergo NIPS. Pregnant women with high‐risk of SCAs underwent prenatal diagnosis and maternal copy number variation sequencing (CNV‐seq). Results Among 117 women with high‐risk of SCAs, 72 accepted prenatal diagnosis, 86 accepted maternal CNV‐seq, and 21 had maternal sex chromosome abnormalities. The abnormality rate was significantly higher than women at low‐risk of SCAs (24.42% vs 3.51%). Using a novel parameter cffDNA (ChrX)/cffDNA, when the ratio was greater than 2, all foetuses had normal karyotype, and 75.0% (6/8) had abnormal maternal chromosome X. If the ratio was less than or equal to 2, only 10% (4/40) of the mothers had chromosome X CNV alterations, while 33.3% (13/40) of their foetuses had sex chromosomes CNV abnormalities. Conclusions Approximately 25% of pregnant women with SCAs predicted by NIPS had sex chromosome abnormalities as determined by CNV‐seq. The ratio of cffDNA (ChrX)/cffDNA can tentatively distinguish the maternal or foetal origin of abnormal cell‐free DNA. In a reanalysis of previous NIPS data, false‐positive results caused by maternal CNV might be elucidated.

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Section: Discussionmentioning

confidence: 96%

High false‐positive non‐invasive prenatal screening results for sex chromosome abnormalities: Are maternal factors the culprit?

et al. 2019

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“…It is efficient and accurate for the identification of the common fetal aneuploidies, especially for chromosomes 13, 18, and 21. Recently, some studies have found that NIPT, through deeper sequencing, can screen for microdeletions and microduplications, which are greater than 300 Kb in fetal genomes [ 17 – 21 ]. However, there have been no previous reports of screening the 17q12 duplication syndrome using NIPT.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive prenatal testing for the detection of fetal chromosome 17 microduplication: clinical implications and findings

Shi,

Zheng,

Wang

et al. 2024

Mol Cytogenet

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Background Noninvasive prenatal testing (NIPT) is widely used to screen for fetal aneuploidies. However, there are few reports of using NIPT for screening chromosomal microduplications and microdeletions. This study aimed to investigate the application efficiency of NIPT for detecting chromosomal microduplications. Methods Four cases of copy number gains on the long arm of chromosome 17 (17q12) were detected using NIPT and further confirmed using copy number variation (CNV) analysis based on chromosome microarray analysis (CMA). Results The prenatal diagnosis CMA results of the three cases showed that the microduplications in 17q12 (ranging from 1.5 to 1.9 Mb) were consistent with the NIPT results. The karyotypic analysis excluded other possible unbalanced rearrangements. The positive predictive value of NIPT for detecting chromosomal 17q12 microduplication was 75.0%. Conclusions NIPT has a good screening effect on 17q12 syndrome through prenatal diagnosis, therefore it could be considered for screening fetal CNV during the second trimester. With the clinical application of NIPT, invasive prenatal diagnoses could be effectively reduced while also improving the detection rate of fetal CNV.

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“…We have known that it is very e cient and accurate for the detection of common fetal chromosome aneuploidy, especially for chromosome 13, 18 and 21. Recently, some studies have found that NIPT through deeper sequencing can screen some microdeletions and microduplications, which are greater than 300 Kb in fetal genomes [18][19][20][21][22] . However, there are no reports of 17q12 duplication syndrome screened by NIPT previously.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Diagnosis of Microduplication of Fetal Chromosome 17 Following Noninvasive Prenatal Testing

Shi

Zheng

Wang

et al. 2021

Preprint

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Background Chromosome 17q12 duplication syndrome is a disease caused by the complete or partial duplication of q12 in the long arm of chromosome 17, there were no cases reported about the prenatal diagnosis of the syndrome. Most of the fetal phenotype of the syndrome may not be evident during the pregnancy, which means the syndrome was only be discovered accidentally or missed during the prenatal examination. Objective Noninvasive prenatal testing (NIPT) is widely used in the screening of common fetal chromosome aneuploidy. However, reports on chromosomal microduplication and microdeletion are rare. The aim of the study was to investigate the application value of NIPT for the detection of chromosomal microduplication. Case presentations: We found two cases of microduplication in the long arm of chromosome 17(17q12), they were first detected by NIPT and then were further diagnosed by copy number variation (CNV) analysis based on chromosome microarray analysis (CMA). The CMA results of prenatal diagnosis showed that the microduplications in 17q12 (one was 1.5Mb, the other was 1.9Mb) were consistent with the NIPT results. The amniotic fluid karyotype analysis showed no abnormalities. Finally, because it was pathogenic copy number variant, both of the parents chose to terminate the pregnancy. Conclusion In the study, two cases of microduplication fragment in the long arm of chromosome 17 were detected by NIPT and were confirmed by CMA. To our knowledge, this is the first report of prenatal diagnosis of chromosome 17q12 duplication syndrome following NIPT. This suggests that NIPT is an effective method to screen chromosome microduplications in prenatal diagnosis, especially for the chromosome 17q12 duplication syndrome.

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Reducing false positive rate of fetal monosomy X in non‐invasive prenatal testing using a combined algorithm to detect maternal mosaic monosomy X

Cited by 5 publications

References 12 publications

High false‐positive non‐invasive prenatal screening results for sex chromosome abnormalities: Are maternal factors the culprit?

High false‐positive non‐invasive prenatal screening results for sex chromosome abnormalities: Are maternal factors the culprit?

Noninvasive prenatal testing for the detection of fetal chromosome 17 microduplication: clinical implications and findings

Prenatal Diagnosis of Microduplication of Fetal Chromosome 17 Following Noninvasive Prenatal Testing

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