Non-invasive prenatal gene diagnosis has been developed rapidly in the recent years, and numerous medical researchers are focusing on it. Such techniques could not only achieve prenatal diagnosis accurately, but also ...Non-invasive prenatal gene diagnosis has been developed rapidly in the recent years, and numerous medical researchers are focusing on it. Such techniques could not only achieve prenatal diagnosis accurately, but also prevent tangential illness in fetuses and thus, reduce the incidence of diseases. Moreover, it is non-invasive prenatal gene diagnosis that prevents potential threaten and danger to both mothers and fetuses. Therefore, it is welcomed by clinical gynecologist and obstetrian, researchers of medical genetics, and especially, pregnancies. This review article touches briefly on the advanced development of using cell-free DNA, RNA in maternal plasma and urine for non-invasive prenatal gene diagnosis.展开更多
The concentration of cell-free fetal DNA fragments should be detected before noninvasive prenatal testing(NIPT).The fetal DNA molecules have significant clinical potential in determining the overall performance of NIP...The concentration of cell-free fetal DNA fragments should be detected before noninvasive prenatal testing(NIPT).The fetal DNA molecules have significant clinical potential in determining the overall performance of NIPT and clinical interpretation.It is important to measure fetal DNA fraction before NIPT.However,there is still little research on how to calculate the concentration of female fetuses.Two estimation approaches were proposed to calculate fetal DNA fraction,including the fragments size-based approach,aneuploid-based approach,which are all approaches based on chromosome segments.Based on high-throughput sequencing data,two approaches to calculate the DNA fraction of male fetuses were tested and obtained the experiment values,which were close to the actual values.The correlation coefficient of fragments size-based approach was 0.9243(P<0.0001)and the aneuploid-based approach reached 0.9339(P<0.0001).We calculated the concentration of female fetuses and obtained remarkable experimental results.We came up with two approaches for calculating the fetal DNA fraction of female fetuses.It provides an important theoretical basis for the detection of female fetal concentration in future clinical diagnosis.展开更多
Objective: The purpose of this study is to review the clinical experience and performance of noninvasive prenatal testing (NIPT) method, using cell-free DNAto detect chromosomes 21, 18, 13, X, and Y abnormalities in o...Objective: The purpose of this study is to review the clinical experience and performance of noninvasive prenatal testing (NIPT) method, using cell-free DNAto detect chromosomes 21, 18, 13, X, and Y abnormalities in over 7910 clinical samples from South Korean population. Method: Pregnant women between 1st of November 2015 to 18th of February 2018, with obstetric clinical findings participated in the study. NIPT was performed based on masivelly parallel sequencing with 0.3× low coverage paired-end sequencing using cell-free DNA in maternal plasma. Further invasive prenatal testing was recommended for pregnant women with positive NIPT results. Results: Of the total 7910 participants, 7890 (99.75%) were tested for NIPT and the remaining 20 (0.25%) were below the Quality Control (QC) standards. T13, T18, XXX, XXY and XYY had 100% of sensitivity, specificity, positive predictive values (PPV) and accuracy. The overall sensitivity was 100% and specificity, PPV and accuracy of all chromosomal abnormalities with further validation were 99.92%, 94.25%, and, 99.92% respectively. Conclusion: Our NIPT results showed high positive predictive value for the detection of autosomal trisomies and sex chromosome aneuploidies in our sample cohort.展开更多
Backgroud Amniotic fluid （AF） supernatant contains cell-free fetal DNA （cffDNA） fragments.This study attempted to take advantage of cffDNA as a new material for prenatal diagnosis,which could be combined with simp...Backgroud Amniotic fluid （AF） supernatant contains cell-free fetal DNA （cffDNA） fragments.This study attempted to take advantage of cffDNA as a new material for prenatal diagnosis,which could be combined with simple quantitative fluorescent polymerase chain reaction （QF-PCR） to provide an ancillary method for the prenatal diagnosis of trisomy 21 syndrome.Methods AF supernatant samples were obtained from 27 women carrying euploid fetuses and 28 women carrying aneuploid fetuses with known cytogenetic karyotypes.Peripheral blood samples of the parents were collected at the same time.Short tandem repeat （STR） fragments on chromosome 21 were amplified by QF-PCR.Fetal condition and the parental source of the extra chromosome could be determined by the STR peaks.Results The sensitivity of the assay for the aneuploid was 93％ （26/28; confidence interval,CI：77％-98％） and the specificity was 100％ （26/26; CI：88％-100％）.The determination rate of the origin of the extra chromosome was 69％.The sensitivity and the specificity of the assay in the euploid were 100％ （27/27）.Conclusions Trisomy 21 can be prenatally diagnosed by the QF-PCR method in AF supernatant.This karyotype analysis method greatly reduces the requirement for the specimen size.It will be a benefit for early amniocentesis and could avoid pregnancy complications.The method may become an ancillary method for prenatal diagnosis of trisomy 21.展开更多
In the last few years,the introduction of cell-free DNA has rapidly altered prenatal screening regimens and is increasingly offered as the second- or,at times,even the first-tier screening test.Should an early anomaly...In the last few years,the introduction of cell-free DNA has rapidly altered prenatal screening regimens and is increasingly offered as the second- or,at times,even the first-tier screening test.Should an early anomaly scan also be part of an up-to-date screening policy? This paper reappraises the value of fetal first-trimester ultrasonography.The primary aims of the first-trimester scan are to establish gestational age based on the measurement of fetal crown-rump length,to detect multiple pregnancy and chorionicity,and to measure fetal nuchal translucency thickness as part of a combined screening test for chromosomal abnormalities.With recent advancements in ultrasound technology,there is compelling evidence that a majority of fetuses with major structural abnormalities and almost half of them without chromosomal abnormalities can be detected in the first trimester.We focused on the first-trimester screening of fetal major defects,especially including fetal congenital heart disease and cleft lip and palate by ultrasound markers and views.Moreover,it is critical to highlight that after a detailed anomaly scan in the first trimester without major structural anomalies and positive genetic tests,the residual chance of favorable outcome in fetuses with isolated increased nuchal translucency is relatively high.The discussion on the role of cell-free DNA in prenatal screening is still ongoing.Even in the event of it becoming a first-line screening test for aneuploidies,the importance of a first-trimester fetal scan,including assessment of markers for other anomalies,remains undisputed.展开更多
Conventional prenatal diagnosis relies on invasive chorionic biopsy or amniocentesis, which increases the risk of miscarriage, and is undertaken at 11-20 weeks gestation.1 The discovery of cell-free fetal DNA in mater...Conventional prenatal diagnosis relies on invasive chorionic biopsy or amniocentesis, which increases the risk of miscarriage, and is undertaken at 11-20 weeks gestation.1 The discovery of cell-free fetal DNA in maternal plasma has, however, offered a new strategy for non-invasive prenatal diagnosis.2 Cell-free fetal DNA in maternal plasma has been used for the determination of fetal gender3 and RHD status4 as well as testing certain monogenic diseases such as 13-thalassemia5 and cystic fibrosis.6 However,展开更多
Background:One inevitable shortcoming of non-invasive prenatal screening(NIPS)/cell-free DNA(cfDNA)sequencing is the uninterpretable(“no-call”)result,which is mainly caused by an insufficient fetal fraction.This stu...Background:One inevitable shortcoming of non-invasive prenatal screening(NIPS)/cell-free DNA(cfDNA)sequencing is the uninterpretable(“no-call”)result,which is mainly caused by an insufficient fetal fraction.This study was performed to investigate the factors associated with a successful second NIPS in these cases and determine the optimal management for women with initial no-call results.Methods:We retrospectively analyzed the data of women who underwent NIPS with initial no-call results due to an insufficient fetal fraction from 2017 to 2019 in our center.We compared these women's maternal and pregnancy information with the data of women who had attained a successful second NIPS result and women who had received no-call results for a second time.Results:Among the 33,684 women who underwent NIPS,137 with a no-call result underwent a retest.Comparison between the 87(63.50%)women with a successful retest and the other 50(36.50%)women showed a significant difference in both the initial fetal fraction and maternal body mass index(BMI),whereas the other factors showed no significant differences.In addition,with an initial fetal fraction of<2.00%,the retest success rate was very limited.Conclusions:We identified two major factors associated with a successful NIPS retest:the initial fetal fraction and the maternal BMI.These findings suggest the need for specialized management for this subset of women and would be instructional for the counseling for these women.展开更多
文摘Non-invasive prenatal gene diagnosis has been developed rapidly in the recent years, and numerous medical researchers are focusing on it. Such techniques could not only achieve prenatal diagnosis accurately, but also prevent tangential illness in fetuses and thus, reduce the incidence of diseases. Moreover, it is non-invasive prenatal gene diagnosis that prevents potential threaten and danger to both mothers and fetuses. Therefore, it is welcomed by clinical gynecologist and obstetrian, researchers of medical genetics, and especially, pregnancies. This review article touches briefly on the advanced development of using cell-free DNA, RNA in maternal plasma and urine for non-invasive prenatal gene diagnosis.
基金supported by the National Key Research and Development Program of China 2016YFC1000307The sub-project of National Key Research and Development Program of China 2016YFC1000307-10the Program of National Research Institute for Family Planning(2017GJM04,2018CNV).
文摘The concentration of cell-free fetal DNA fragments should be detected before noninvasive prenatal testing(NIPT).The fetal DNA molecules have significant clinical potential in determining the overall performance of NIPT and clinical interpretation.It is important to measure fetal DNA fraction before NIPT.However,there is still little research on how to calculate the concentration of female fetuses.Two estimation approaches were proposed to calculate fetal DNA fraction,including the fragments size-based approach,aneuploid-based approach,which are all approaches based on chromosome segments.Based on high-throughput sequencing data,two approaches to calculate the DNA fraction of male fetuses were tested and obtained the experiment values,which were close to the actual values.The correlation coefficient of fragments size-based approach was 0.9243(P<0.0001)and the aneuploid-based approach reached 0.9339(P<0.0001).We calculated the concentration of female fetuses and obtained remarkable experimental results.We came up with two approaches for calculating the fetal DNA fraction of female fetuses.It provides an important theoretical basis for the detection of female fetal concentration in future clinical diagnosis.
文摘Objective: The purpose of this study is to review the clinical experience and performance of noninvasive prenatal testing (NIPT) method, using cell-free DNAto detect chromosomes 21, 18, 13, X, and Y abnormalities in over 7910 clinical samples from South Korean population. Method: Pregnant women between 1st of November 2015 to 18th of February 2018, with obstetric clinical findings participated in the study. NIPT was performed based on masivelly parallel sequencing with 0.3× low coverage paired-end sequencing using cell-free DNA in maternal plasma. Further invasive prenatal testing was recommended for pregnant women with positive NIPT results. Results: Of the total 7910 participants, 7890 (99.75%) were tested for NIPT and the remaining 20 (0.25%) were below the Quality Control (QC) standards. T13, T18, XXX, XXY and XYY had 100% of sensitivity, specificity, positive predictive values (PPV) and accuracy. The overall sensitivity was 100% and specificity, PPV and accuracy of all chromosomal abnormalities with further validation were 99.92%, 94.25%, and, 99.92% respectively. Conclusion: Our NIPT results showed high positive predictive value for the detection of autosomal trisomies and sex chromosome aneuploidies in our sample cohort.
文摘Backgroud Amniotic fluid （AF） supernatant contains cell-free fetal DNA （cffDNA） fragments.This study attempted to take advantage of cffDNA as a new material for prenatal diagnosis,which could be combined with simple quantitative fluorescent polymerase chain reaction （QF-PCR） to provide an ancillary method for the prenatal diagnosis of trisomy 21 syndrome.Methods AF supernatant samples were obtained from 27 women carrying euploid fetuses and 28 women carrying aneuploid fetuses with known cytogenetic karyotypes.Peripheral blood samples of the parents were collected at the same time.Short tandem repeat （STR） fragments on chromosome 21 were amplified by QF-PCR.Fetal condition and the parental source of the extra chromosome could be determined by the STR peaks.Results The sensitivity of the assay for the aneuploid was 93％ （26/28; confidence interval,CI：77％-98％） and the specificity was 100％ （26/26; CI：88％-100％）.The determination rate of the origin of the extra chromosome was 69％.The sensitivity and the specificity of the assay in the euploid were 100％ （27/27）.Conclusions Trisomy 21 can be prenatally diagnosed by the QF-PCR method in AF supernatant.This karyotype analysis method greatly reduces the requirement for the specimen size.It will be a benefit for early amniocentesis and could avoid pregnancy complications.The method may become an ancillary method for prenatal diagnosis of trisomy 21.
文摘In the last few years,the introduction of cell-free DNA has rapidly altered prenatal screening regimens and is increasingly offered as the second- or,at times,even the first-tier screening test.Should an early anomaly scan also be part of an up-to-date screening policy? This paper reappraises the value of fetal first-trimester ultrasonography.The primary aims of the first-trimester scan are to establish gestational age based on the measurement of fetal crown-rump length,to detect multiple pregnancy and chorionicity,and to measure fetal nuchal translucency thickness as part of a combined screening test for chromosomal abnormalities.With recent advancements in ultrasound technology,there is compelling evidence that a majority of fetuses with major structural abnormalities and almost half of them without chromosomal abnormalities can be detected in the first trimester.We focused on the first-trimester screening of fetal major defects,especially including fetal congenital heart disease and cleft lip and palate by ultrasound markers and views.Moreover,it is critical to highlight that after a detailed anomaly scan in the first trimester without major structural anomalies and positive genetic tests,the residual chance of favorable outcome in fetuses with isolated increased nuchal translucency is relatively high.The discussion on the role of cell-free DNA in prenatal screening is still ongoing.Even in the event of it becoming a first-line screening test for aneuploidies,the importance of a first-trimester fetal scan,including assessment of markers for other anomalies,remains undisputed.
文摘Conventional prenatal diagnosis relies on invasive chorionic biopsy or amniocentesis, which increases the risk of miscarriage, and is undertaken at 11-20 weeks gestation.1 The discovery of cell-free fetal DNA in maternal plasma has, however, offered a new strategy for non-invasive prenatal diagnosis.2 Cell-free fetal DNA in maternal plasma has been used for the determination of fetal gender3 and RHD status4 as well as testing certain monogenic diseases such as 13-thalassemia5 and cystic fibrosis.6 However,
基金supported by grants from the National Key R&D Program of China(No.2018YFC1002402)the Nanjing Outstanding Youth Grant for Medical Science and Technology(No.JQX18008).
文摘Background:One inevitable shortcoming of non-invasive prenatal screening(NIPS)/cell-free DNA(cfDNA)sequencing is the uninterpretable(“no-call”)result,which is mainly caused by an insufficient fetal fraction.This study was performed to investigate the factors associated with a successful second NIPS in these cases and determine the optimal management for women with initial no-call results.Methods:We retrospectively analyzed the data of women who underwent NIPS with initial no-call results due to an insufficient fetal fraction from 2017 to 2019 in our center.We compared these women's maternal and pregnancy information with the data of women who had attained a successful second NIPS result and women who had received no-call results for a second time.Results:Among the 33,684 women who underwent NIPS,137 with a no-call result underwent a retest.Comparison between the 87(63.50%)women with a successful retest and the other 50(36.50%)women showed a significant difference in both the initial fetal fraction and maternal body mass index(BMI),whereas the other factors showed no significant differences.In addition,with an initial fetal fraction of<2.00%,the retest success rate was very limited.Conclusions:We identified two major factors associated with a successful NIPS retest:the initial fetal fraction and the maternal BMI.These findings suggest the need for specialized management for this subset of women and would be instructional for the counseling for these women.
