OBJECTIVE: To explore the cause for a twin pregnancy with false negative result for 22q11.2 deletion syndrome by expanded non-invasive prenatal testing (NIPT-plus). METHODS: A pregnant woman with twin pregnancy through in-vitro fertilization and negative result of NIPT-plus was selected as the study subject. Amniocentesis was conducted after ultrasonic finding of fetal abnormalities. In addition to conventional G-banded karyotyping, copy number variation sequencing (CNV-Seq) was used to detect chromosomal microdeletion and microduplication. Clinical data of the woman were analyzed to explore the reasons underlying the false negative result. RESULTS: NIPT-plus has yielded a negative result with 11.77 Mb unique reads and 3.05% fetal fraction. Both fetuses had a normal karyotype (46,XY and 46,XX). CNV-seq indicated that one of the fetuses was normal, whilst the other was diagnosed with a 2.58 Mb deletion in the 22q11.2 region. CONCLUSION The false negative result may be attributed to the combined influence of low fetal fraction, high BMI, twin pregnancy through IVF and a relatively small deletion fragment. Ultrasonography exam following a low-risk result of NIPT-plus should not be neglected.
Pregnancy ; Female ; Humans ; Prenatal Diagnosis ; Pregnancy, Twin/genetics* ; DiGeorge Syndrome/genetics* ; DNA Copy Number Variations ; Amniocentesis

OBJECTIVE: To carry out genetic analysis for a fetus with confined placental mosaicism (CPM) for trisomy 2 (T2) in conjunct with fetal uniparental disomy (UPD). METHODS: Amniocentesis and chromosomal karyotyping was carried out for a pregnant woman with a high risk for chromosome 2 anomalies indicated by non-invasive prenatal testing (NIPT). Single nucleotide polymorphism array (SNP-array) and trio-whole exome sequencing (Trio-WES) were carried out. Ultrasonography was used to closely monitor the fetal growth. Multifocal sampling of the placenta was performed after delivery for copy number variation sequencing (CNV-seq). RESULTS: The fetus was found to have a normal chromosomal karyotype. SNP-array has revealed multiple regions with loss of heterozygosity (LOH) on chromosome 2. Trio-WES confirmed the presence of maternal UPD for chromosome 2. Ultrasonography has revealed intrauterine growth restriction and oligohydramnios. Intrauterine fetal demise had occurred at 23⁺⁴ weeks of gestation. Pathological examination had failed to find salient visceral abnormality. The placenta was proved to contain complete T2 by CNV-seq. CONCLUSION T2 CPM can cause false positive result for NIPT and may be complicated with fetal UPD, leading to adverse obstetric outcomes such as intrauterine growth restriction, oligohydramnios and intrauterine fetal demise.
Female ; Humans ; Pregnancy ; Amniocentesis ; Chromosomes, Human, Pair 2/genetics* ; DNA Copy Number Variations ; Fetal Death ; Fetal Growth Retardation/genetics* ; Fetus ; Mosaicism ; Oligohydramnios ; Placenta ; Trisomy/genetics* ; Uniparental Disomy/genetics*

OBJECTIVE: To explore the genetic basis for a fetus with severe heart defect and mosaic trisomy 12, and the correlation between chromosomal abnormalities and clinical manifestations and pregnancy outcome. METHODS: A 33-year-old pregnant woman who presented at Lianyungang Maternal and Child Health Care Hospital on May 17, 2021 due to abnormal fetal heart development revealed by ultrasonography was selected as the study subject. Clinical data of the fetus were collected. Amniotic fluid sample of the pregnant women was collected and subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). The CNKI, WanFang and PubMed databases were searched with key words, with the retrieval period set as from June 1, 1992 to June 1, 2022. RESULTS: For the 33-year-old pregnant woman, ultrasonography at 22+6 gestational weeks had revealed abnormal fetal heart development and ectopic pulmonary vein drainage. G-banded karyotyping showed that the fetus has a karyotype of mos 47,XX,+12[1]/46,XX[73], with the mosaicism rate being 1.35%. CMA results suggested that about 18% of fetal chromosome 12 was trisomic. A newborn was delivered at 39 weeks of gestation. Follow-up confirmed severe congenital heart disease, small head circumference, low-set ears and auricular deformity. The infant had died 3 months later. The database search has retrieved 9 reports. Literature review suggested that the liveborn infants with mosaic trisomy 12 had diverse clinical manifestations depending on the affected organs, which had included congenital heart disease and/or other organs and facial dysmorphisms, resulting in adverse pregnancy outcomes. CONCLUSION Trisomy 12 mosaicism is an important factor for severe heart defects. The results of ultrasound examination have important value for evaluating the prognosis of the affected fetuses.
Infant, Newborn ; Child ; Pregnancy ; Female ; Humans ; Adult ; Trisomy/genetics* ; Amniocentesis/methods* ; Chromosome Disorders ; Mosaicism ; Fetus ; Heart Defects, Congenital/genetics*

OBJECTIVE: To explore the genetic etiology of 5 cases of monochorionic-diamniotic (MCDA) with genetic discordance. METHODS: 148 cases of MCDA twins who were diagnosed by amniocentesis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 2016 to June 2020 were selected as the study subjects. Relevant clinical data of the pregnant women were collected, and amniotic fluid samples of the twins were collected separately. Chromosomal karyotyping analysis and single nucleotide polymorphism array (SNP array) assay were carried out. RESULTS: The results of chromosomal karyotyping analysis showed that 5 of the MCDA twins had inconsistent chromosome karyotypes, with an incidence of 3.4% (5/148). SNP array assay showed that 3 fetuses were mosaics. CONCLUSION Genetic discordance occurs among MCDA twins, and prenatal counseling for such cases should be given by doctors with experience in medical genetics and fetal medicine, and personalized clinical management should be recommended.
Child ; Pregnancy ; Female ; Humans ; China ; Twins/genetics* ; Amniocentesis ; Karyotyping ; Fetus ; Twins, Monozygotic/genetics* ; Ultrasonography, Prenatal ; Retrospective Studies

OBJECTIVE: To report on a case of mosaicism 13q inversion duplication, analyze its mechanism, and discuss the correlation between its genotype and phenotype. METHODS: Amniotic fluid and umbilical cord blood were collected at 23 and 32 weeks of gestation, respectively. Combined with G-banding chromosome karyotyping analysis, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) were used to confirm the result. RESULTS: The karyotype of the fetus was determined as 47,XY,+inv dup(13)(q14.3q34)/46,XY. After careful counseling, the couple decided to continue with the pregnancy, and had given birth to a boy at 40 weeks' gestation. Except for a red plaque (hemangioma) on the nose bridge, no obvious abnormality (intelligence to be evaluated) was discovered. CONCLUSION To provide reference for clinical genetic counseling and risk assessment, the location and proportion of new centromere formation should be fully considered in the case of mosaicism 13q inversion duplication.
Amniocentesis ; Chromosome Inversion/genetics* ; Comparative Genomic Hybridization ; Female ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Mosaicism ; Pregnancy ; Prenatal Diagnosis

The standardized medical genetics residency training in China has started late and differed from foreign training systems with no ready-made experience for reference. Started from 2014, the development of medical genetics residency training has encountered difficulties in enrollment, poor basic knowledge, and difficulties in completing the training tasks. Through a series of teaching reforms such as to offer elective courses to undergraduates, employment of flexible and diverse teaching forms such as MOOC, provision of high simulation amniocentesis model for professional skill training, and establishment of a sound teacher training system, our institution has expanded the choice for medical students' career direction and improved the core competency of medical genetics residency trainees.
Humans ; Female ; Pregnancy ; Internship and Residency ; Genetics, Medical ; Amniocentesis ; China ; Computer Simulation

OBJECTIVE: To review the clinical data of a fetus with false positive result of non-invasive prenatal testing (NIPT) due to confined placental mosaicism (CPM). METHODS: Amniotic fluid sample was taken from a pregnant women with high risk for chromosome 16 aneuploidy for karyotyping analysis, single nucleotide polymorphism array (SNP array) and interphase fluorescence in situ hybridization (FISH). Genetic testing was also conducted on the fetal and maternal surface of the placenta, root of umbilical cord and fetal skin tissue after induced abortion. RESULTS: Cytogenetic analysis of the amniotic fluid sample yielded a normal karyotype. SNP array revealed mosaicism (20%) of trisomy 16 in the fetus. FISH confirmed the presence of mosaicism (25%) for trisomy 16. After induced labor, all sampled sites of placenta were confirmed to contain trisomy 16 by SNP array, while the analysis of fetal skin tissue yielded a negative result. CONCLUSION CPM is an important factor for false positive NIPT result. Prenatal identification of CPM and strengthened pregnancy management are important to reduce adverse pregnancy outcomes.
Amniocentesis ; Chromosomes, Human, Pair 16/genetics* ; Cytogenetic Analysis ; Female ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Molecular Biology ; Mosaicism ; Placenta ; Pregnancy ; Prenatal Diagnosis ; Trisomy/genetics*

OBJECTIVE: To assess the value of non-invasive prenatal testing based on cfDNA barcode-enabled single-molecule test (cfBEST) for the prenatal diagnosis of oculocutaneous albinism type I in a family. METHODS: Prenatal genetic diagnosis was carried out by using the cfBEST-based method as well as invasive prenatal diagnosis through amniocentesis. The outcome of the pregnancy was followed up. RESULTS: Non-invasive prenatal testing based on cfBEST showed a fetal DNA concentration of 6.6%, with the proportion of c.929_930insC (p.Arg311Lysfs*7) and c.1037-7T>A mutations being 45.7% and 0%, respectively. The posterior frequency of the negative results was 1, suggesting that the fetus carried neither of the two mutations. The result was consistent with that of invasive prenatal diagnosis, and the follow-up found that the fetus was normal. CONCLUSION Non-invasive prenatal testing based on cfBEST can be used to detect maternal and fetal genotypes in maternal cell-free DNA, which is clinically feasible.
Albinism ; Albinism, Oculocutaneous/genetics* ; Amniocentesis ; Cell-Free Nucleic Acids ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis

BACKGROUND: We aimed to investigate whether various immune-related plasma proteins, alone or in combination with conventional clinical risk factors, can predict spontaneous preterm delivery (SPTD) and intra-amniotic infection in women with premature cervical dilation or a short cervix (≤ 25 mm).METHODS: This retrospective study included 80 asymptomatic women with premature cervical dilation (n = 50) or a short cervix (n = 30), who underwent amniocentesis at 17–29 weeks. Amniotic fluid (AF) was cultured, and maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and complements C3a and C5a, using enzyme-linked immunosorbent assay (ELISA) kits. The primary outcome measures were SPTD at < 32 weeks and positive AF cultures.RESULTS: The plasma levels of IL-6, C3a, and C5a, but not of MMP-9 and TIMP-1, were significantly higher in women with SPTD at < 32 weeks than in those who delivered at ≥ 32 weeks. The women who delivered at < 32 weeks had more advanced cervical dilatation, and higher rates of antibiotic and tocolytic administration and were less likely to be given vaginal progesterone than those who delivered at ≥ 32 weeks. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma IL-6 and C3a levels, and cervical dilatation (area under the curve [AUC], 0.901). The AUC for this model was significantly greater than that for any single variable included in the predictive model. In the univariate analysis, plasma IL-6 level was the only significant predictor of intra-amniotic infection.CONCLUSION: In women with premature cervical dilation or a short cervix, maternal plasma IL-6, C3a, and C5a levels could be useful non-invasive predictors of SPTD at < 32 weeks. A combination of these biomarkers and conventional clinical factors may clearly improve the predictability for SPTD, as compared with the biomarkers alone. An increased plasma level of IL-6 predicted intra-amniotic infection.
Amniocentesis ; Amniotic Fluid ; Area Under Curve ; Biomarkers ; Blood Proteins ; Cervix Uteri ; Complement System Proteins ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-6 ; Interleukins ; Labor Stage, First ; Outcome Assessment (Health Care) ; Plasma ; Pregnancy ; Progesterone ; Retrospective Studies ; Risk Factors ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinases

OBJECTIVE: To explore the suitable process for prenatal screening and diagnosis for women with advanced maternal age. METHODS: From January 2014 to November 2017, the indications and distributions of prenatal diagnosis for women with advanced maternal age only or accompanying with positive maternal serum test screening and non-invasive prenatal testing (NIPT), abnormal fetal ultrasound, one harboring chromosomal abnormalities or anomalous reproductive history were analyzed. The rate of fetal chromosomal abnormalities was compared between different groups. RESULTS: The 351 pregnant women with fetal chromosomal abnormalities have included 196 cases with advanced maternal age, 26 with positive maternal serum test, 96 with high-risk by NIPT, 14 with abnormal fetal ultrasound, 15 with one partner harboring chromosomal abnormalities, and 4 with anomalous reproductive history. Assuming that all pregnant women had undergone maternal serum test screening or NIPT without amniocentesis, the detection rate of fetal chromosome abnormality would be 51.0% and 69.2%, respectively. However, should these women have received both tests, the detection rate would be as high as 84.6%. Should those with one partner harboring chromosomal abnormalities undergone maternal serum test screening or NIPT without amniocentesis, the detection rate of fetal chromosomal abnormality would only be 6.7%. CONCLUSION Should pregnant women with advanced maternal age undergo both maternal serum test and NIPT, the detection rate of fetal chromosomal abnormality will be higher than those receiving only maternal serum test screening or NIPT. Couples with one partner harboring chromosomal abnormalities should undergo prenatal diagnosis by amniocentesis.
Amniocentesis ; Chromosome Aberrations ; Chromosome Disorders ; Female ; Humans ; Maternal Age ; Pregnancy ; Prenatal Diagnosis