OBJECTIVE: To explore the application value of artificial intelligence (AI)-assisted chromosomal karyotype analysis in the diagnosis of prenatal chromosomal mosaicism. METHODS: A retrospective analysis was conducted on 172 pregnant women who underwent amniocentesis at the Department of Medical Genetics and Prenatal Diagnosis, the Third Affiliated Hospital of Zhengzhou University between January 2019 and December 2024. All cases whose fetuses were diagnosed with chromosomal mosaicism via karyotype analysis and stratified into two groups based on the analytical software employed: the conventional analysis group (n = 70), which utilized Leica analysis software for karyotype image recognition and cell counting; and the AI-assisted analysis group (n = 102), which utilized AI-assisted software for the same procedures. The clinical performance of AI-assisted karyotype analysis in diagnosing chromosomal mosaicism was comprehensively evaluated by comparing the types of mosaic karyotypes, distribution of mosaic ratios, and verification outcomes of different detection modalities between the two groups. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-406-01). RESULTS: No statistically significant difference was observed in baseline characteristics (maternal age, gestational week, and indications for prenatal diagnosis) between the two groups. Regarding the detection efficacy for numerical and structural mosaicisms, no significant difference was found in the detection of numerical mosaicism. However, the conventional analysis group exhibited a significantly higher detection rate of autosomal structural mosaicism compared to the AI-assisted group (11.43% vs. 0.98%, P < 0.05). Numerical mosaicism cases were further verified using copy number variation sequencing (CNV-seq) and/or fluorescence in situ hybridization (FISH). The AI-assisted group demonstrated a significantly lower inconsistency rate (5.56% vs. 20.41%, P < 0.05) compared to the conventional group. For low-proportion (< 10%) chromosomal mosaicism, the AI-assisted group had a significantly lower detection rate (13.25% vs. 29.69%, P < 0.05). Subsequent validation of low-proportion mosaicism by CNV-seq and/or FISH showed a higher consistency rate in the AI-assisted group (81.82% vs. 54.55%), though the difference did not reach statistical significance (P = 0.360). CONCLUSION For the karyotyping analysis of prenatal chromosomal mosaicism, AI-assisted karyotype analysis shows high accuracy and consistency in identifying numerical chromosomal mosaicism, particularly in reducing the detection of low-proportion (< 10%) mosaicism while improving verification accuracy. AI-assisted analysis can significantly improve the detection accuracy of numerical mosaicism and mitigate the risk of misclassification for low-proportion (< 10%) mosaicism, thereby providing more precise clinical evidence for the prenatal diagnosis of chromosomal mosaicisms.
Humans ; Female ; Mosaicism ; Pregnancy ; Karyotyping/methods* ; Artificial Intelligence ; Prenatal Diagnosis/methods* ; Adult ; Retrospective Studies ; Chromosome Disorders/genetics* ; Amniocentesis

OBJECTIVE: To report on a case of mosaicism involving trisomy 21, maternal uniparental isodisomy, and normal diploid cells in uncultured amniocytes, and to explore the discrepancies between conventional cytogenetic and molecular cytogenetic techniques during prenatal diagnosis. METHODS: A 30-year-old pregnant woman who presented to Boai Hospital of Zhongshan on June 27, 2023 has undergone amniocentesis at 16 weeks of gestation. The amniotic fluid sample was subjected to quantitative fluorescent PCR (QF-PCR), G-banded karyotype analysis, and chromosomal microarray analysis (CMA). The discrepancies between the results of each method were analyzed. This study was approved by Medical Ethics Committee of Boai Hospital of Zhongshan (Ethics No.: KY-2024-001-01). RESULTS: Non-invasive prenatal testing (NIPT) at 12 weeks indicated a high risk of trisomy 21. QF-PCR of uncultured amniocytes revealed a pattern of trisomy 21. After one week of cell culture, G-banding analysis showed mos 47,XX,+21[1]/46,XX[72]. CMA revealed a homozygous state of chromosome 21 in cultured cells, while uncultured amniocytes showed mosaic trisomy 21 with an estimated proportion of 50%. These findings suggested a complex chromosomal mosaicism in the fetus, which may result from a trisomy rescue event during early embryogenesis, leading to coexistence of three cell lines including trisomy 21, maternal uniparental isodisomy, and normal diploid cells. CONCLUSION In prenatal diagnosis, discrepancies may arise between QF-PCR and conventional chromosomal karyotyping analysis, particularly in complex genetic phenomena such as trisomy rescue and uniparental disomy. For cases where NIPT indicated a high risk of trisomy 21 but G-banding karyotype analysis yielded a normal result, further molecular genetic testing using uncultured cells is recommended.
Humans ; Female ; Mosaicism ; Pregnancy ; Uniparental Disomy/diagnosis* ; Adult ; Down Syndrome/diagnosis* ; Prenatal Diagnosis/methods* ; Diploidy ; Karyotyping ; Amniocentesis

OBJECTIVE: To investigate the characteristics of chromosomal abnormalities in amniotic fluid among pregnant women in Liangshan Prefecture and explore strategies for optimizing prenatal diagnosis. METHODS: A retrospective analysis was conducted on 1 024 amniocentesis samples collected at the Prenatal Diagnosis Center of Liangshan Prefecture Maternal and Child Health Care Hospital between February 2022 and December 2024. Chromosome karyotyping analysis (3 cases had failed culture, 1 021 valid samples) was combined with high-throughput chromosome sequencing analysis (CNV-seq) for the detection. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-07). RESULTS: The overall detection rate of chromosomal karyotype abnormalities in the amniotic fluid cells was 4.02% (41/1 021), with numerical abnormalities accounting for 80.49% (33/41) and structural abnormalities for 19.51% (8/41). Numerical abnormalities were primarily trisomy 21 (16/41, 39.02%) and 47,XXY (6/41, 14.63%). Structural abnormalities included translocations (6 cases) and mosaicism (2 cases). CNV-seq detected 22 pathogenic or likely pathogenic copy number variations, whilst the undetection rate for balanced translocations reached 100% (7/7). The combined application of karyotyping and CNV-seq, leveraging complementary strengths, can enhance the overall detection rate. CONCLUSION The distribution characteristics of chromosomal abnormalities in amniotic fluid from pregnant women in Liangshan exhibit regional specificity. A combined testing strategy significantly optimizes prenatal diagnosis efficacy, providing crucial evidence for enhancing the effectiveness of prenatal diagnosis in ethnic minority regions.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Retrospective Studies ; Adult ; Amniotic Fluid ; Karyotyping ; Amniocentesis ; Chromosome Disorders/genetics* ; China ; High-Throughput Nucleotide Sequencing ; DNA Copy Number Variations/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*

OBJECTIVETo explore the reason for discordant results of karyotyping and microarray analysis in a fetus with mosaic tetrasomy 9p.

METHODSAmniocentesis was carried out for a pregnant woman with advanced age for whom ultrasound scan has indicated fetal ventricular expansion, intrauterine growth retardation and persistent upper venous cavity. G-banded karyotyping and single nucleotide polymorphism-based arrays (SNP-array) analysis were performed at the same time.

RESULTSAnalysis of amniocytic chromosome has suggested mosaic tetrasomy 9p (47,XX,+psu idic(9)(q21)[23]/46,XX[27]). While SNP-array has detected a non-mosaic trisomy 9p with a 68.7 Mb duplication at 9p24.3q21.11. The results of the two methods were therefore discordant.

CONCLUSIONSNP-array will analyze genetic material in the form of numbers rather than morphology. For chimeras containing two types of cell lines, when the mosaic rate was close to 50% and the average amount of genetic material of the chimeras was equivalent to the amount of genetic material of non-chimeras, microarray analysis may come to the conclusion of a non-mosaic heteroploidy. Therefore, microarray results for large segment chromosome abnormalities should be combined with the results of G-banded karyotyping for genetic counseling.

Adult ; Amniocentesis ; methods ; Aneuploidy ; Chromosome Banding ; Chromosome Disorders ; diagnosis ; genetics ; Chromosomes, Human, Pair 9 ; Diagnostic Errors ; Female ; Fetal Growth Retardation ; diagnosis ; genetics ; Humans ; Infant, Newborn ; Karyotyping ; Male ; Mosaicism ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide ; Pregnancy ; Pregnancy Outcome ; Trisomy

OBJECTIVETo compare the results of fluorescence in situ hybridization (FISH) assay and conventional karyotyping analysis for the detection of chromosomal aneuploidies.

METHODSIn total 2607 amniotic fluid samples were subjected to an improved FISH technique. Meanwhile, karyotype analysis was also ordered for each sample.

RESULTSOf the 2607 samples, 62 abnormalities were identified by FISH, which included 62 cases of trisomy 21, 5 cases of 45,X, 12 cases of trisomy 18, 3 cases of trisomy 13, and 1 case of 47, XYY. Conventional karyotyping analysis has identified 63 cases of trisomy 21, 5 cases of 45,X, 12 cases of trisomy 18, 3 cases of trisomy 13, 1 case of 47, XYY, and 57 cases of balanced translocations. The success rate of FISH detection was 98.4% for trisomy 21, and 100% for 45,X, trisomy 18 and trisomy 13.

CONCLUSIONFor the detection of chromosomal aneuploidies, FISH assay is quick, simple, accurate and can reduce workload when aminocyte culture has failed. As an auxiliary method for amniocytic analysis, it can provide reference for the consultation of those with advanced age and high pregnancy risk.

Adult ; Amniocentesis ; methods ; Amniotic Fluid ; cytology ; metabolism ; Chromosomes, Human, Pair 18 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Y ; genetics ; Down Syndrome ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotype ; Karyotyping ; methods ; Middle Aged ; Pregnancy ; Reproducibility of Results ; Sensitivity and Specificity ; Sex Chromosome Aberrations ; Trisomy ; genetics ; Trisomy 18 Syndrome ; Turner Syndrome ; genetics ; Young Adult

OBJECTIVETo assess the safety of repeated invasive prenatal diagnosis primarily due to failed culture of amniotic cells.

METHODSBetween January 2000 and October 2012, 167 cases required repeated invasive prenatal diagnosis among a total of 5304 amniocentesis cases. Clinical outcome and karyotypes were analyzed to calculate the rate of fetal loss.

RESULTSFor the 167 re-sampled cases, the indications have included failed amniocyte culture (121 cases), chromosome mosaicisms (23 cases), failed amniocentesis (21 cases), and request for confirmation (2 cases). No fetal loss has occurred. All samples were cultured successfully. Fourteen cases (8.38%) have been found with an abnormal karyotype. Four mosaic trisomic cases (2 mosaic trisomy 16, 1 mosaic trisomy 20, and 1 mosaic trisomy 8) were verified to be normal.

CONCLUSIONRepeated invasive prenatal diagnosis does not increase the rate of fetal loss. It can be recommended to cases with failed amniocyte culture. Caution should be undertaken when counseling prenatally detected mosaicism trisomies.

Adult ; Amniocentesis ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Karyotyping ; methods ; Middle Aged ; Pregnancy ; Prenatal Diagnosis ; methods ; Trisomy ; Young Adult

OBJECTIVE: To evaluate the safety, effectiveness and complications of serial invasive prenatal diagnostic techniques, and to investigate the prenatal diagnosis indication as well as to analyze the abnormal chromosomal karyotype. METHODS: We retrospectively studied all patients from March 2005 to May 2012 who received amniocentesis and cordocentesis in the prenatal diagnosis center of Second Xiangya Hospital. The indication of the procedure, successful rate and complications were evaluated, and 25 abnormal chromosome nuclear types were analyzed. RESULTS: A total of 669 patients received invasive prenatal diagnosis from March 2005 to May 2012 in Second Xiangya Hospital: 598 received amniocentesis and 71 cordocentesis carried out. Compared with the cordocentesis group, the amniocentesis group had higher achievement ratio (91.54% vs 100%, P<0.05), lower spontaneous abortion rate (1.41% vs 0.33%, P<0.05), fewer abnormal karyotypes (11.27% vs 2.84%, P<0.05) and lower expenditure (880 yuan vs 800 yuan, P<0.05). Positive screening, advanced maternal age, and ultrasonography abnormality were the top 3 indications of amniocentesis and cordocentesis. We found 25 abnormal karyotypes, including 6 cases of trisomy 21, 4 sex chromosomal abnormalities, 7 autosomal balanced translocations, 1 marker chromosome, and 7 mosaics. CONCLUSION As a widely used invasive prenatal diagnosis, amniocentesis is safe and effective. The complications of cordocentesis are much higher than those of amniocentesis, which is not a proper routine procedure for prenatal diagnosis of abnormal karyotype. The analysis of karyotype not only can identify fetal chromosome abnormality, but also provide the scientific basis for pregnancy continuation, thus reducing the ratio of birth defect.
Abnormal Karyotype ; statistics & numerical data ; Adult ; Amniocentesis ; methods ; Cordocentesis ; adverse effects ; methods ; Evaluation Studies as Topic ; Female ; Humans ; Karyotyping ; methods ; Pregnancy ; Prenatal Diagnosis ; methods ; Retrospective Studies

OBJECTIVETo determine the feasibility and accuracy of detecting numerical chromosomal abnormalities by high-flux sequencing analysis of free fetal DNA from maternal plasma.

METHODSHigh-flux sequencing was applied to analyze fetal chromosome sequence copy numbers in 153 pregnant women. Fetal karyotyping was also carried out on amniocentesis samples.

RESULTSSix cases were detected with fetal chromosomal abnormalities by high-flux sequencing analysis, among which five were confirmed by karyotyping to be chromosomal aneuploidies (47,XYY; 45,X; 47,XY,+18; 47,XY,+21 and 47,XY,+13), 1 case was confirmed to be structural rearrangement, i.e., 46,XY,der(13;21)(q10;q10),+21. Furthermore, 3 chromosomal polymorphisms (one 46,XY,21p+ and two 46,XY,Yqh-) were identified. The two methods yielded similar results on fetal chromosome copy number detection.

CONCLUSIONHigh-flux sequencing analysis of free DNA derived from maternal plasma is efficient for detecting fetal chromosomal aneuploidies, and is non-invasive, highly sensitive and specific. It therefore has a broad application in antenatal diagnosis.

Adult ; Amniocentesis ; methods ; Aneuploidy ; Chromosome Disorders ; diagnosis ; genetics ; DNA ; chemistry ; genetics ; Female ; Fetus ; Humans ; Pregnancy ; Prenatal Diagnosis ; methods ; Young Adult

OBJECTIVETo analyze the aberrant der(X) chromosome using conventional and molecular cytogenetic approaches in a fetus of second trimester and to discuss its clinical effect.

METHODSConventional cytogenetic procedures (GTG and CBG banding) were performed on cultured amniotic fluid cells. Three-color fluorescence in situ hybridization (FISH) consisting of X chromosome enumeration probes(CEPX), CEPY and Tel Xp/Yp was further performed to study the aberrant der(X) chromosome.

RESULTSDer(X) was a rare X/Y translocation. The final karyotypes of the fetus was designated as: 46,X,der(X)t(X;Y)(p22.3;q11.2). ish der(X)t(X;Y)(p22.3;q11.2)(X/Ypter-, DXZ1+, DYZ1+)mat.

CONCLUSIONThe combination of FISH and conventional cytogenetic techniques is a powerful tool to determine derivative chromosome and to offer an accurate genetic counseling. Identification of Xp; Yq rearrangement can help estimate the risk of fetus abnormalities and give a more precise prognosis.

Adult ; Amniocentesis ; methods ; Amniotic Fluid ; cytology ; Chromosome Aberrations ; Chromosome Banding ; methods ; Chromosomes, Human, X ; Cytogenetic Analysis ; methods ; Female ; Fetus ; abnormalities ; Genetic Counseling ; methods ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Pregnancy ; Pregnancy Trimester, Second