Objective:To analyze the clinical data and results of prenatal diagnosis for fetuses with high-risk for trisomy/monosomy 13 by non-invasive prenatal testing (NIPT).Methods:Clinical data of pregnant women with fetus at a high risk for trisomy/monosomy 13 by NIPT at the First Affiliated Hospital of Zhengzhou University from May 2016 to May 2024 were reviewed, and relevant data such as Z-score, positive predictive value (PPV) and fetal fraction (FF) were analyzed to assess the correlation between them. This study was approved by the Ethics Committee of the Hospital (No. 2018-YB-08). Results:71 fetuses were found to have a high risk by NIPT, including 58 cases for trisomy 13 (T13) and 13 cases for monosomy 13 (M13). 52 women had opted invasive prenatal diagnosis and 13 cases were confirmed, which yielded a positive prediction value (PPV) of 25%. 12 fetuses were confirmed as T13 (PPV = 29.3%; 12/41), 1 was confirmed as M13 (PPV = 9.1%; 1/11). The PPV had increased along with the Z-score. Fetal faction (FF) was not correlated with the age of woman but gestational age, and was negatively correlated with the body mass index. No statistical difference was found in FF and Z-score between true- and false-positive fetuses, and there was a weak correlation between the Z-score and FF. The PPV of the NIPT could be improved by combining the results of ultrasonography. Conclusion:The high false positive rate for T13 may be related to confined placental mosaicism, PPV is related to the Z-score, which in turn is related to FF. High-risk women are strongly recommended to undergo genetic counseling and prenatal diagnosis. Clinicians should consider relevant information such as the age of women, gestational age, indication for prenatal screening, Z-score, PPV, and FF in order to accurately interpret the result of NIPT, reduce anxiety, and avoid direct termination of the pregnancy.

OBJECTIVE: To analyze the clinical data and results of prenatal diagnosis for fetuses with high-risk for trisomy/monosomy 13 by non-invasive prenatal testing (NIPT). METHODS: Clinical data of pregnant women with fetus at a high risk for trisomy/monosomy 13 by NIPT at the First Affiliated Hospital of Zhengzhou University from May 2016 to May 2024 were reviewed, and relevant data such as Z-score, positive predictive value (PPV) and fetal fraction (FF) were analyzed to assess the correlation between them. This study was approved by the Ethics Committee of the Hospital (No. 2018-YB-08). RESULTS: 71 fetuses were found to have a high risk by NIPT, including 58 cases for trisomy 13 (T13) and 13 cases for monosomy 13 (M13). 52 women had opted invasive prenatal diagnosis and 13 cases were confirmed, which yielded a positive prediction value (PPV) of 25%. 12 fetuses were confirmed as T13 (PPV = 29.3%; 12/41), 1 was confirmed as M13 (PPV = 9.1%; 1/11). The PPV had increased along with the Z-score. Fetal faction (FF) was not correlated with the age of woman but gestational age, and was negatively correlated with the body mass index. No statistical difference was found in FF and Z-score between true- and false-positive fetuses, and there was a weak correlation between the Z-score and FF. The PPV of the NIPT could be improved by combining the results of ultrasonography. CONCLUSION The high false positive rate for T13 may be related to confined placental mosaicism, PPV is related to the Z-score, which in turn is related to FF. High-risk women are strongly recommended to undergo genetic counseling and prenatal diagnosis. Clinicians should consider relevant information such as the age of women, gestational age, indication for prenatal screening, Z-score, PPV, and FF in order to accurately interpret the result of NIPT, reduce anxiety, and avoid direct termination of the pregnancy.
Humans ; Female ; Pregnancy ; Trisomy 13 Syndrome/genetics* ; Adult ; Prenatal Diagnosis/methods* ; Noninvasive Prenatal Testing/methods*

Objective:To evaluate the screening efficacy and clinical management strategies of cell-free fetal DNA (cffDNA) for copy number variations (CNVs) at 16p13.11-p12.3.Methods:Clinical data of 35 fetuses with high-risk indications for 16p13.11-p12.3 variations identified by non-invasive prenatal test (NIPT) at the First Affiliated Hospital of Zhengzhou University between September 2018 and December 2023 were retrospectively analyzed. Amniocentesis was performed to obtain fetal samples, followed by validation through chromosomal karyotyping and CNV-sequencing. The variant size, genetic origin, and pregnancy outcomes were systematically assessed. Statistical analysis was conducted using Pearson's Chi-square test or Fisher's exact test. Results:(1) Screening efficacy: The overall positive predictive value (PPV) of cffDNA was 45.8% (11/24), with a PPV of 4/8 for deletions and 7/16 for duplications. The false-positive rate was 54.2% (13/24), including one case complicated by a Robertsonian translocation [45,XY,rob(21;22)]. (2) Genetic characteristics: Among confirmed variants, 8/11 were inherited (six maternal duplications, one paternal deletion), while 3/11 were de novo (one deletion and two of undetermined origin). (3) Clinical outcomes: Among live births, 3/9 confirmed cases exhibited abnormal manifestations, including conductive hearing loss (one case with maternal duplication), language developmental delay (one case with 16p13.11 tetrasomy combined with trisomy), and hypotonia (one case with de novo deletion). Follow-up of false-negative or undiagnosed fetuses (22 cases) and 6/9 of confirmed cases showed no abnormalities. Conclusion:CNVs at 16p13.11-p12.3 demonstrate significant incomplete penetrance. Invasive diagnosis combined with familial analysis is recommended for cffDNA-positive cases. Genetic counseling should emphasize variant size and parental origin, and long-term neurodevelopmental follow-up mechanisms should be established for confirmed fetuses.

Objective:To analyze the clinical data and results of prenatal diagnosis for fetuses with high-risk for trisomy/monosomy 13 by non-invasive prenatal testing (NIPT).Methods:Clinical data of pregnant women with fetus at a high risk for trisomy/monosomy 13 by NIPT at the First Affiliated Hospital of Zhengzhou University from May 2016 to May 2024 were reviewed, and relevant data such as Z-score, positive predictive value (PPV) and fetal fraction (FF) were analyzed to assess the correlation between them. This study was approved by the Ethics Committee of the Hospital (No. 2018-YB-08). Results:71 fetuses were found to have a high risk by NIPT, including 58 cases for trisomy 13 (T13) and 13 cases for monosomy 13 (M13). 52 women had opted invasive prenatal diagnosis and 13 cases were confirmed, which yielded a positive prediction value (PPV) of 25%. 12 fetuses were confirmed as T13 (PPV = 29.3%; 12/41), 1 was confirmed as M13 (PPV = 9.1%; 1/11). The PPV had increased along with the Z-score. Fetal faction (FF) was not correlated with the age of woman but gestational age, and was negatively correlated with the body mass index. No statistical difference was found in FF and Z-score between true- and false-positive fetuses, and there was a weak correlation between the Z-score and FF. The PPV of the NIPT could be improved by combining the results of ultrasonography. Conclusion:The high false positive rate for T13 may be related to confined placental mosaicism, PPV is related to the Z-score, which in turn is related to FF. High-risk women are strongly recommended to undergo genetic counseling and prenatal diagnosis. Clinicians should consider relevant information such as the age of women, gestational age, indication for prenatal screening, Z-score, PPV, and FF in order to accurately interpret the result of NIPT, reduce anxiety, and avoid direct termination of the pregnancy.

Objective:To evaluate the screening efficacy and clinical management strategies of cell-free fetal DNA (cffDNA) for copy number variations (CNVs) at 16p13.11-p12.3.Methods:Clinical data of 35 fetuses with high-risk indications for 16p13.11-p12.3 variations identified by non-invasive prenatal test (NIPT) at the First Affiliated Hospital of Zhengzhou University between September 2018 and December 2023 were retrospectively analyzed. Amniocentesis was performed to obtain fetal samples, followed by validation through chromosomal karyotyping and CNV-sequencing. The variant size, genetic origin, and pregnancy outcomes were systematically assessed. Statistical analysis was conducted using Pearson's Chi-square test or Fisher's exact test. Results:(1) Screening efficacy: The overall positive predictive value (PPV) of cffDNA was 45.8% (11/24), with a PPV of 4/8 for deletions and 7/16 for duplications. The false-positive rate was 54.2% (13/24), including one case complicated by a Robertsonian translocation [45,XY,rob(21;22)]. (2) Genetic characteristics: Among confirmed variants, 8/11 were inherited (six maternal duplications, one paternal deletion), while 3/11 were de novo (one deletion and two of undetermined origin). (3) Clinical outcomes: Among live births, 3/9 confirmed cases exhibited abnormal manifestations, including conductive hearing loss (one case with maternal duplication), language developmental delay (one case with 16p13.11 tetrasomy combined with trisomy), and hypotonia (one case with de novo deletion). Follow-up of false-negative or undiagnosed fetuses (22 cases) and 6/9 of confirmed cases showed no abnormalities. Conclusion:CNVs at 16p13.11-p12.3 demonstrate significant incomplete penetrance. Invasive diagnosis combined with familial analysis is recommended for cffDNA-positive cases. Genetic counseling should emphasize variant size and parental origin, and long-term neurodevelopmental follow-up mechanisms should be established for confirmed fetuses.

OBJECTIVE: To summarize the results of prenatal diagnosis and outcome of pregnancy of fetuses with a high risk for 6p22.1.1-p21.32 duplication signaled by non-invasive prenatal screening (NIPS). METHODS: Clinical information, results of prenatal diagnosis and pregnancy for fetuses with a high risk for 6p22.1-p21.32 duplication were collected and analyzed. This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethic No. 2018-YB-08). RESULTS: Forty three pregnant women with a high risk for 6p22.1-p21.32 duplication were identified by NIPS, among whom 30 had accepted invasive prenatal diagnosis, and 27 fetuses were verified to be false positive. Three fetuses were found to have other chromosomal abnormalities, among whom two were rated to be likely benign CNV and 1 was rated to be likely pathogenic. Follow up of the 43 pregnant women revealed that 35 fetuses were normal after birth, 1 pregnancy was terminated, and 7 were lost to follow up. CONCLUSION For pregnant women with a high risk for 6p22.1-p21.32 duplication signaled by NIPS, genetic counselor need to inform them the high false positive rate and recommend invasive prenatal diagnosis and/or ultrasound examination in order to reduce the psychological and economic burdens.
Humans ; Female ; Pregnancy ; Chromosome Duplication ; Adult ; Prenatal Diagnosis/methods* ; Chromosomes, Human, Pair 6/genetics* ; Pregnancy Outcome ; Noninvasive Prenatal Testing/methods* ; Chromosome Disorders/genetics* ; Fetus/abnormalities*

Objective:To explore the genetic etiology of a child with delayed growth and development and carry out a literature review.Methods:A child suspected for Al Kaissi syndrome at the First Affiliated Hospital of Zhengzhou University on March 6, 2021 was selected as the study subject. Following extraction of genomic DNA, the child was subjected to copy number variation sequencing (CNV-seq) and whole exome sequencing (WES), and candidate variants were verified by PCR-agarose gel electrophoresis and quantitative real-time PCR (qPCR). Prenatal diagnosis was conducted on chorionic villi sample upon subsequent pregnancy.Results:The child, a 6-year-and-4-month-old boy, has dysmorphic features including low-set protruding ears and triangular face, delayed language and intellectual development, and ventricular septal defect. CNV-seq result has found no obvious abnormality, whilst WES revealed homozygous deletion of exons 1 and 2 of the CDK10 gene, which was confirmed by PCR -agarose gel electrophoresis and qPCR. Both of his parents were heterozygous carriers. Prenatal diagnosis using chorionic villi samples suggested that the fetus also carried the heterozygous deletion.Conclusion:The clinical features of Al Kaissi syndrome in this child can probably be attributed to the homozygous deletion of exons 1 and 2 of the CDK10 gene.

Clinical application of serological screening and non-invasive prenatal testing (NIPT) both have difficulties to attain high detection rate and low cost. For its advantages of high detection rate, high sensitivity, simplicity, short turnaround time and low cost, digital PCR (dPCR) has provided a new choice for prenatal screening of trisomies 21, 18 and 13. To standardize the application of dPCR for prenatal screening, we have formulated this consensus by referring to relevant guidelines, expert consensus and latest literature, which has covered the basic requirements, application scope, pre-testing service, testing procedure, report interpretation, genetic counseling, and limitations for this technology.

Objective:To summarize the results of prenatal diagnosis and outcome of pregnancy of fetuses with a high risk for 6p22.1-p21.32 duplication signaled by non-invasive prenatal screening (NIPS).Methods:Clinical information, results of prenatal diagnosis and pregnancy for fetuses with a high risk for 6p22.1-p21.32 duplication were collected and analyzed. This study has been approved by the medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethic No.2018-YB-08).Results:Forty three pregnant women with a high risk for 6p22.1-p21.32 duplication were identified by NIPS, among whom 30 had accepted invasive prenatal diagnosis, and 27 fetuses were verified to be false positive. Three fetuses were found to have other chromosomal abnormalities, among whom two were rated to be likely benign CNV and 1 was rated to be likely pathogenic. Follow up of the 43 pregnant women revealed that 35 fetuses were normal after birth, 1 pregnancy was terminated, and 7 were lost to follow up.Conclusion:For pregnant women with a high risk for 6p22.1-p21.32 duplication signaled by NIPS, genetic counselor need to inform them the high false positive rate and recommend invasive prenatal diagnosis and/or ultrasound examination in order to reduce the psychological and economic burdens.

Objective:To summarize the results of prenatal diagnosis and outcome of pregnancy of fetuses with a high risk for 6p22.1-p21.32 duplication signaled by non-invasive prenatal screening (NIPS).Methods:Clinical information, results of prenatal diagnosis and pregnancy for fetuses with a high risk for 6p22.1-p21.32 duplication were collected and analyzed. This study has been approved by the medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethic No.2018-YB-08).Results:Forty three pregnant women with a high risk for 6p22.1-p21.32 duplication were identified by NIPS, among whom 30 had accepted invasive prenatal diagnosis, and 27 fetuses were verified to be false positive. Three fetuses were found to have other chromosomal abnormalities, among whom two were rated to be likely benign CNV and 1 was rated to be likely pathogenic. Follow up of the 43 pregnant women revealed that 35 fetuses were normal after birth, 1 pregnancy was terminated, and 7 were lost to follow up.Conclusion:For pregnant women with a high risk for 6p22.1-p21.32 duplication signaled by NIPS, genetic counselor need to inform them the high false positive rate and recommend invasive prenatal diagnosis and/or ultrasound examination in order to reduce the psychological and economic burdens.