An efficient method for noninvasive prenatal diagnosis of fetal trisomy 13, trisomy 18, and trisomy 21

Introduction: Prenatal diagnosis of trisomy 21, 18 and 13 plays a very important role in the improving population quality. This study was aimed at (1) Identifying the prevalence of trisomy 21, 18 and 13 by QFPCR from amniotic cells of high-risk pregnancies; and (2) Evaluating the association between diagnosed trisomies and some characteristics of mother and fetus. Objectives and methods: 170 pregnant women with high risk of having trisomy 21, 18 or 13 fetuses during first trimester screening (gestation age from 11 weeks to 13 weeks 6 days). DNA was extracted from amniocytes for prenatal diagnosis using QF-PCR. Results: The prevalence of trisomies was 9.4%, among which trisomy 21 and trisomy 18 accounted for 68.8% and 31.2%, respectively; none of them was trisomy 13. There was the significant association between diagnosed trisomies and maternal age (cut-off 30.5 years old) and nuchal translucency thickness (cut-off 1.95 mm). MoM median of free β-hCG increased in trisomy 21 group (4.35, p = 0.021) and decreased in trisomy 18 group (0.13, p < 0.001) as compared to the non-trisomy group (2.28). MoM median of serum PAPP-A decreased in trisomy 18 group (0.14, p = 0.004) as compared to the non-trisomy group (0.54). Conclusion: Prenatal diagnosis by QF-PCR detected remarkable prevalence of fetuses with trisomy 21 và 18. There was the significant association between diagnosed trisomies and maternal age, nuchal translucency thickness, free β-hCG and serum PAPP-A. Key words: prenatal diagnosis, trisomy, QF-PCR

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44 Single-Nucleotide Polymorphisms Expressed by Placental RNA: Assessment for Use in Noninvasive Prenatal Diagnosis of Trisomy 21

Clinical Chemistry ◽

10.1373/clinchem.2007.093146 ◽

2007 ◽

Vol 53 (12) ◽

pp. 2223-2224 ◽

Cited By ~ 15

Author(s):

Attie TJI Go ◽

Allerdien Visser ◽

Monique AM Mulders ◽

Marinus A Blankenstein ◽

John MG van Vugt ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Single Nucleotide Polymorphisms ◽

Trisomy 21 ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Noninvasive Prenatal Diagnosis

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Using Patient-Centered Care After a Prenatal Diagnosis of Trisomy 18 or Trisomy 13

JAMA Pediatrics ◽

10.1001/jamapediatrics.2016.4798 ◽

2017 ◽

Vol 171 (4) ◽

pp. 382 ◽

Cited By ~ 12

Author(s):

Shelly Haug ◽

Mitchell Goldstein ◽

Denise Cummins ◽

Elba Fayard ◽

T. Allen Merritt

Keyword(s):

Prenatal Diagnosis ◽

Patient Centered Care ◽

Trisomy 18 ◽

Trisomy 13 ◽

Patient Centered ◽

Centered Care

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Noninvasive Prenatal Detection of Trisomy 21 by an Epigenetic–Genetic Chromosome-Dosage Approach

Clinical Chemistry ◽

10.1373/clinchem.2009.134114 ◽

2010 ◽

Vol 56 (1) ◽

pp. 90-98 ◽

Cited By ~ 85

Author(s):

Yu K Tong ◽

Shengnan Jin ◽

Rossa WK Chiu ◽

Chunming Ding ◽

KC Allen Chan ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Genetic Markers ◽

Blood Cells ◽

Trisomy 21 ◽

Maternal Blood ◽

Maternal Plasma ◽

Plasma Samples ◽

Prenatal Detection ◽

Fetal Dna ◽

Noninvasive Prenatal Diagnosis

Abstract Background: The use of fetal DNA in maternal plasma for noninvasive prenatal diagnosis of trisomy 21 (T21) is an actively researched area. We propose a novel method of T21 detection that combines fetal-specific epigenetic and genetic markers. Methods: We used combined bisulfite restriction analysis to search for fetal DNA markers on chromosome 21 that were differentially methylated in the placenta and maternal blood cells and confirmed any target locus with bisulfite sequencing. We then used methylation-sensitive restriction endonuclease digestion followed by microfluidics digital PCR analysis to investigate the identified marker. Chromosome-dosage analysis was performed by comparing the dosage of this epigenetic marker with that of the ZFY (zinc finger protein, Y-linked) gene on chromosome Y. Results: The putative promoter of the HLCS (holocarboxylase synthetase) gene was hypermethylated in the placenta and hypomethylated in maternal blood cells. A chromosome-dosage comparison of the hypermethylated HLCS and ZFY loci could distinguish samples of T21 and euploid placental DNA. Twenty-four maternal plasma samples from euploid pregnancies and 5 maternal plasma samples from T21 pregnancies were analyzed. All but 1 of the euploid samples were correctly classified. Conclusions: The epigenetic–genetic chromosome-dosage approach is a new method for noninvasive prenatal detection of T21. The epigenetic part of the analysis can be applied to all pregnancies. Because the genetic part of the analysis uses paternally inherited, fetal-specific genetic markers that are abundant in the genome, broad population coverage should be readily achievable. This approach has the potential to become a generally usable technique for noninvasive prenatal diagnosis.

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Prenatal Diagnosis of Trisomy 13 or Trisomy 18 Survey

PsycTESTS Dataset ◽

10.1037/t74492-000 ◽

2018 ◽

Author(s):

Stephanie E. Wallace ◽

Sara Gilvary ◽

Michael J. Smith ◽

Siobhan M. Dolan

Keyword(s):

Prenatal Diagnosis ◽

Trisomy 18 ◽

Trisomy 13

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Noninvasive Prenatal Detection of Fetal Trisomy 18 by Epigenetic Allelic Ratio Analysis in Maternal Plasma: Theoretical and Empirical Considerations

Clinical Chemistry ◽

10.1373/clinchem.2006.076851 ◽

2006 ◽

Vol 52 (12) ◽

pp. 2194-2202 ◽

Cited By ~ 117

Author(s):

Yu K Tong ◽

Chunming Ding ◽

Rossa WK Chiu ◽

Ageliki Gerovassili ◽

Stephen SC Chim ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Maternal Plasma ◽

Trisomy 18 ◽

Ratio Analysis ◽

Dna Mixtures ◽

Allelic Ratio ◽

Fetal Dna ◽

Noninvasive Prenatal Diagnosis ◽

Cell Free Fetal Dna ◽

Chromosomal Aneuploidies

Abstract Background: The discovery of cell-free fetal DNA in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. However, the use of maternal plasma fetal DNA for the direct detection of fetal chromosomal aneuploidies has not been reported. We postulate that the aneuploidy status of a fetus could be revealed by an epigenetic allelic ratio approach, i.e., by analyzing the allelic ratio of a single-base variation present within DNA molecules exhibiting a placental-specific epigenetic signature in maternal plasma. Methods: Placental-derived fetal-specific unmethylated maspin (SERPINB5) promoter sequences on human chromosome 18 were detectable in placental–maternal DNA mixtures and in maternal plasma by bisulfite modification followed by methylation-specific PCR (MSP) and primer extension. The ratios between the extension products of the 2 alleles were calculated for heterozygous placentas, placental–maternal blood cell DNA mixtures, and maternal plasma samples. The allelic ratios were compared between pregnancies carrying trisomy 18 and euploid fetuses. Results: The epigenetic allelic ratios of all tested trisomy 18 samples deviated from the reference range obtained from euploid samples (placental DNA, 1.135 to 2.052; placental–maternal DNA mixtures, 1.170 to 1.985; maternal plasma, 0.330 to 3.044; without skew correction on the raw mass spectrometric data). A theoretical model was established and validated that predicted that a minimum of 200 copies of genomic DNA after bisulfite conversion were required for distinguishing euploid and aneuploid fetuses with confidence. Conclusion: Epigenetic allelic ratio analysis of maternal plasma DNA represents a promising approach for noninvasive prenatal diagnosis of fetal chromosomal aneuploidies.

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Maternal Plasma DNA Analysis with Massively Parallel Sequencing by Ligation for Noninvasive Prenatal Diagnosis of Trisomy 21

Clinical Chemistry ◽

10.1373/clinchem.2009.136507 ◽

2010 ◽

Vol 56 (3) ◽

pp. 459-463 ◽

Cited By ~ 99

Author(s):

Rossa WK Chiu ◽

Hao Sun ◽

Ranjit Akolekar ◽

Christopher Clouser ◽

Clarence Lee ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Trisomy 21 ◽

Massively Parallel Sequencing ◽

Maternal Plasma ◽

Chromosome 21 ◽

Massively Parallel ◽

Plasma Dna ◽

Parallel Sequencing ◽

Noninvasive Prenatal Diagnosis ◽

Sequencing By Synthesis

Abstract Background: Noninvasive prenatal diagnosis of trisomy 21 (T21) has recently been shown to be achievable by massively parallel sequencing of maternal plasma on a sequencing-by-synthesis platform. The quantification of several other human chromosomes, including chromosomes 18 and 13, has been shown to be less precise, however, with quantitative biases related to the chromosomal GC content. Methods: Maternal plasma DNA from 10 euploid and 5 T21 pregnancies was sequenced with a sequencing-by-ligation approach. We calculated the genomic representations (GRs) of sequenced reads from each chromosome and their associated measurement CVs and compared the GRs of chromosome 21 (chr21) for the euploid and T21 pregnancies. Results: We obtained a median of 12 × 106 unique reads (21% of the total reads) per sample. The GRs deviated from those expected for some chromosomes but in a manner different from that previously reported for the sequencing-by-synthesis approach. Measurements of the GRs for chromosomes 18 and 13 were less precise than for chr21. z Scores of the GR of chr21 were increased in the T21 pregnancies, compared with the euploid pregnancies. Conclusions: Massively parallel sequencing-by-ligation of maternal plasma DNA was effective in identifying T21 fetuses noninvasively. The quantitative biases observed among the GRs of certain chromosomes were more likely based on analytical factors than biological factors. Further research is needed to enhance the precision for measuring for the representations of chromosomes 18 and 13.

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Bất thường nhiễm sắc thể trên thai nhi dị tật tim bẩm sinh

Tạp chí Phụ sản ◽

10.46755/vjog.2018.1.699 ◽

2018 ◽

Vol 16 (1) ◽

pp. 52-57

Author(s):

Hai Nam Bui ◽

Danh Cuong Tran

Keyword(s):

Trisomy 21 ◽

Trisomy 18 ◽

Trisomy 13

Bệnh tim bẩm sinh (BTBS) là những bất thường trong cấu trúc tim và các mạch máu lớn xuất hiện trong khi mang thai ở tháng thứ 2 – 3 của thai kỳ. Có tỷ lệ 4 – 14/1000 trẻ đẻ ra sống. BTBS thai nhi có thể chẩn đoán trước sinh bằng siêu âm một cách chính xác. Một số BTBS có kèm theo bất thường nhiễm sắc thể (NST). Do vậy việc kết hợp xét nghiệm sàng lọc và các xét nghiệm di truyền để phát hiện sớm các bất thường NST. Mục tiêu: Mô tả đặc điểm bất thường nhiễm sắc thể ở thai nhi có dị tật tim bẩm sinh. Đối tượng và phương pháp nhiên cứu: Thực hiện ở 92 thai phụ có thai nhi bị bất thường tim, được chọc hút dịch ối làm xét nghiệm NST đồ. Kết quả nghiên cứu: Tỷ lệ BTBS thường gặp trong nghiên cứu là thông liên thất (39,1%), tứ chứng Fallot (26,1%), bệnh ống nhĩ thất (10,9%). Tỷ lệ bất thường NST ở những trường hợp BTBS là 29/92 (31,5%). Trong đó bất thường số lượng NST 25/29 (86,2%) vớitrisomy 18 là 12/29 (41,4%), trisomy 21 là 8/29(27,6%), trisomy 13 là 3/29 (10,34%); Bất thường cấu trúc NST có 4 trường hợp trong đó 2 trường hợp vi mất đoạn 22q11.2 (hội chứng DiGeorge). Kết luận: BTBS có mối liên quan với bất thường NST, các bất thường hay gặp trisomy 13, trisomy 18, trisomy 21 và hội chứng DiGeorge.

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Ứng dụng kỹ thuật BoBs để phát hiện một số hội chứng mất đoạn nhỏ và lệch bội nhiễm sắc thể thai trong chẩn đoán thai nhi có siêu âm bất thường hệ tim mạch

Tạp chí Phụ sản ◽

10.46755/vjog.2018.1.696 ◽

2018 ◽

Vol 16 (1) ◽

Author(s):

Thi Ngoc Lan Hoang ◽

Danh Cuong Tran ◽

Duc Thang Bui ◽

Phuong Thao Le

Keyword(s):

Trisomy 21 ◽

Trisomy 18 ◽

Trisomy 13

Mục tiêu: Đánh giá giá trị kỹ thuật BoBs trong phát hiện một số hội chứng mất đoạn nhỏ và lệch bội nhiễm sắc thể của thai có siêu âm bất thường hệ tim mạch. Đối tượng và phương pháp nghiên cứu: 100 mẫu dịch ối của các thai phụ có thai ≥ 16 tuần và thai có hình ảnh siêu âm bất thường hệ tim mạch được xét nghiệm bằng kỹ thuật BoBs và xét nghiệm nhiễm sắc thể (NST). Kết quả: Phát hiện 28/100 thai có bất thường NST trong đó 8 trường hợp liên quan với vi mất đoạn hoặc nhân đoạn nhỏ NST chỉ được phát hiện bằng kỹ thuật BoBs (5 DiGeorge, 1 Cri-du-chat, 1 Prader Willi/ Anggelman, 1 trisomy 1phần NST 18 (q22.1q22.2) và 20 trường hợp lệch bội NST được phát hiện cả bằng BoBs và xét nghiệm NST thường quy gồm 10 trường hợp Trisomy 21, 9 trisomy 18, 1 trisomy 13. 4/5 thai DiGeorge có tứ chứng Fallot, còn 1 DiGeorge, 1 Prader Willi/Anggelman và 1 nhân đoạn nhỏ NST 18 (q22.1q22.2) có thông liên thất, 1 Cri-duchat có bất thường hệ thống mạch máu. Kết luận: Với các thai có bất thường hệ tim mạch nên sử dụng đồng thời cả 2 kỹ thuật (karyotype và kỹ thuật BoBs) để tăng tỷ lệ phát hiện các bất thường NST đặc biệt các vi mất đoạn NST hay nhân đoạn nhỏ NST và giúp chẩn đoán nhanh, chính xác và tránh bỏ sót nhiều trường hợp bất thường.

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