Detection Rate Of Chromosomal Abnormalities Research Articles

Chromosomal Abnormalities Detected by Chromosomal Microarray Analysis and Karyotype in Fetuses with Ultrasound Abnormalities.

Chromosomal microarray analysis (CMA) is a first-line test to assess the genetic etiology of fetal ultrasound abnormalities. The aim of this study was to evaluate the effectiveness of CMA in detecting chromosomal abnormalities in fetuses with ultrasound abnormalities, including structural abnormalities and non-structural abnormalities. A retrospective study was conducted on 368 fetuses with abnormal ultrasound who received interventional prenatal diagnosis at Meizhou People's Hospital from October 2022 to December 2023. Samples of villi, amniotic fluid, and umbilical cord blood were collected according to different gestational weeks, and karyotype and CMA analyses were performed. The detection rate of chromosomal abnormalities in different ultrasonic abnormalities was analyzed. There were 368 fetuses with abnormal ultrasound, including 114 (31.0%) with structural abnormalities, 225 (61.1%) with non-structural abnormalities, and 29 (7.9%) with structural combined with non-structural abnormalities. The detection rate of aneuploidy and pathogenic (P)/likely pathogenic (LP) copy number variations (CNVs) of CMA in fetuses with structural abnormalities was 5.26% (6/114), the detection rate of karyotype was 2.63% (3/114), and the additional diagnosis rate of CMA was 2.63%. In the fetuses with ultrasonic non-structural abnormalities, the detection rate of karyotype was 6.22% (14/225), the detection rate of aneuploidy and P/LP CNVs in fetuses with ultrasonic structural abnormalities was 9.33% (21/225), and the additional diagnosis rate of CMA was 3.11%. There was no significant difference in chromosome abnormality detection rate of CMA among structural abnormality, non-structural abnormality, and structural abnormality combined with non-structural abnormality groups (5.3%, 9.3%, and 13.8%, p = 0.241), also among multiple ultrasonic abnormality and single ultrasonic abnormality groups (14.8%, and 7.3%, p = 0.105). CMA can significantly improve the detection rate of genetic abnormalities in prenatal diagnosis of ultrasonic abnormal fetuses compared with karyotype analysis. CMA is a more effective tool than karyotyping alone in detecting chromosomal abnormalities in fetuses with ultrasound abnormalities.

Evaluation the Application of Karyotype Analysis and Chromosome Microarray in Prenatal Diagnosis.

We aimed to compare the difference of the chromosomal abnormalities using karyotype analysis and chromosomal microarray (CMA) as well as to evaluate their application in different prenatal diagnosis indications. Overall, 3007 pregnant women with prenatal diagnosis indications from Medical Genetics Department of Linyi Women and Children's Health Care Hospital, who underwent standard G-banded karyotype analysis and CMA, were enrolled from 2018-2022. G-banded karyotype analysis and CMA were undergone simultaneously. All fetuses with genetic variants were enrolled for further analyzing. The frequency and differences of chromosomal abnormalities of the two methods were compared in different prenatal diagnosis indications groups. CMA improved 4.09% (123/3007) of genetic changes compared karyotype analysis. CMA is on par with karyotyping for detection of aneuploidies and gross unbalanced rearrangements. Serological screening and ultrasound abnormalities were the main indications of prenatal diagnosis. The detection rate of chromosomal abnormalities was highest in non-invasive prenatal testing (NIPT) abnormal group. In the ultrasound abnormality group, the detection rate of genetic variants in nuchal translucency (NT) increased group was higher than other subgroups and there was statistically significant difference in the detection rate of pCNVs. CMA can detect 5.57% (40/718) more genetic abnormalities in ultrasound abnormality group on the normal karyotype. CMA improved 0.67% (20/3007) of genetic changes with clinically significant compared karyotype, brought 3.42% (103/3007) of variants with uncertain significance (VOUS). CMA identified additional, clinically significant genetic variants on the basis of normal karyotype analysis, brought a proportion of unclear significant variants. All the pregnant women accepted amniocentesis should be informed about their characteristics of karyotype analysis and CMA by genetic counselors.

The genetics and clinical outcomes in 151 cases of fetal growth restriction: A Chinese single-center study

ObjectiveTo determine the detection rate of chromosomal abnormalities and pregnancy outcomes in fetuses with intrauterine growth restriction.Study designA total of 151 fetal samples with intrauterine growth restriction were divided into the isolated fetal growth restriction (FGR) group, FGR group with structural malformation, and FGR group with non-structural malformation, according to ultrasound abnormalities. The enrolled patients were divided into an early onset FGR group (<32 weeks) and a late-onset FGR group (≥32 weeks). Chromosomal karyotype and microarray analyses were performed and pregnancy outcomes were monitored.ResultsThe karyotypes of 122 patients were analyzed. Four patients exhibited abnormal chromosome numbers or structures. Variations in copy number were detected in 151 cases; 19 cases were found to have chromosomal abnormalities, with a positivity rate of 12.6 %. There was one trisomy in 18 cases, one trisomy in 21 cases, eight pathogenic copy number variations (CNVs), and nine CNVs of unknown clinical significance. The detection rate of FGR combined with structural malformation was significantly higher than that of isolated FGR group. The detection rate of FGR with structural malformations was significantly higher than that with non-structural malformations. The positive detection rate in the FGR group was similar to that in the FGR group with non-structural malformations, with no statistical significance. Chromosomal abnormalities were detected in 17 patients with early onset FGR, with a positivity rate of 13.8 %. Two cases of chromosomal abnormalities were detected in the late-onset FGR group, with a positive rate of 7.1 %, with no statistical significance. A total of 151 fetuses with FGR were followed up for pregnancy outcomes, resulting in 36 cases of pregnancy termination and 13 cases of loss to follow-up. Among the 102 delivered fetuses, six exhibited delayed growth and development, one presented with hypospadias, and another failed the hearing screening. The remaining 94 fetuses demonstrated normal growth and development.ConclusionsThis study confirms the value of CNV detection in fetuses and dynamic ultrasound monitoring for fetuses with intrauterine growth restriction.

Prenatal diagnosis and pregnancy outcomes in fetuses with ventriculomegaly.

Genetic etiology plays a critical role in fetal ventriculomegaly (VM). However, the studies on chromosomal copy number variants (CNVs) in fetal VM are limited. This study aimed to investigate the chromosomal CNVs in fetuses with mild to moderate VM, and explore its genotype-phenotype correlation. A total of 242 fetuses with mild to moderate VM detected by prenatal ultrasound were enrolled in our study from October 2018 to October 2022. All cases underwent chromosomal microarray analysis (CMA) and G-banding simultaneously. All VM cases were classified different subgroups according to the maternal age, severity, VM distribution and presence/absence of other ultrasound abnormalities. The pregnancy outcomes and health conditions after birth were followed up. We also performed a pooled analysis regarding likely pathogenic and pathogenic CNVs (LP/P CNVs) for VM. The detection rate of chromosomal abnormalities by karyotyping was 9.1% (22/242), whereas it was 16.5% (40/242) when CMA was conducted (P < 0.05). The total detection rate of chromosomal abnormalities by karyotyping and CMA was 21.1% (51/242). A 12.0% incremental yield of CMA over karyotyping was observed. The detection rate of total genetic variants in fetuses with bilateral VM was significantly higher than in fetuses with unilateral VM (30.0% vs. 16.7%, P = 0.017). No significant differences were discovered between isolated VM and non-isolated VM, or between mild and moderate VM, or between advanced maternal age (AMA) and non-AMA (all P > 0.05). 28 fetuses with VM were terminated and 214 fetuses were delivered: one presented developmental delay and one presented congenital heart disease. The VM cases with both positive CMA and karyotypic results had a higher rate of termination of pregnancy than those with either a positive CMA or karyotypic result, or both negative testing results (P < 0.001). The combination of CMA and karyotyping should be adopted to improve the positive detection rate of chromosomal abnormalities for VM. The total genetic abnormalities detected using both techniques would affect the final pregnancy outcomes. LP/P CNVs at 16p11.2, 17p13, and 22q11.21 were identified as the top three chromosomal hotspots associated with VM, which would enable genetic counselors to provide more precise genetic counseling for VM pregnancies.

Prenatal ultrasound diagnosis and quality control of fetal nuchal translucency.

In clinical ultrasound examinations, it is challenging to perform quality control on the images of each fetal nuchal translucency (NT) and crown-rump length (CRL). However, small measurement differences can increase the probability of false-positive or false-negative diagnosis. Therefore, it is necessary to establish a quality control system for fetal NT examination. This study aims to control the quality of fetal NT and CRL measurements, evaluate the accuracy of ultrasound physicians in early pregnancy NT measurements, and analyze the impact of increased fetal structure screening on the detection rate of chromosomal abnormalities. Data were collected from cases before and after 12 months of NT examination quality control, with 2 214 before quality control and 2 538 cases after quality control. Three quality control data metrics were analyzed: NT multiple of median (NT-MoM), standard deviation (SD) of log10MoM [(SD) log10MoM], and the slope of NT on CRL (SNC). The performance of NT measurements was monitored through the individual CRL NT-MoM within the 0.9-1.1 MoM range of the normal median curve, while grouped based on different years of experience (<3 years, 3-6 years, >6 years), and NT-MoM values among these groups were compared. Data on NT thickening, structural anomalies, and chromosomal abnormalities were retrospectively analyzed during the quality control period. According to the curve equation of the American NTQR project group, the NT-MoM value before quality control was 0.921 7 MoM, the (SD) log10MoM value was 0.091 92, and the SNC value was 12.20%. After quality control, the NT-MoM value was 0.948 3 MoM, the (SD) log10MoM value was 0.094 81, and the SNC value was 11.43%. The comparison of NT-MoM values before and after quality control showed a statistically significant difference (P<0.000 1). The comparison of NT-MoM values measured by ultrasound physicians with different years of experience before and after quality control also showed statistically significant differences (P<0.000 1). The NT-MoM values for the 3-6 years and >6 years groups were higher after quality control (P<0.05), while the <3 years group showed no significant difference before and after quality control (P>0.05). After quality control, cases of NT thickening without significant structural abnormalities accounted for 19.05%, NT thickening with structural abnormalities accounted for 47.62%, and NT normal with structural abnormalities accounted for 33.33%. There were 36 cases of fetal heart abnormalities, accounting for 20.34% of the total abnormality rate, with a positive rate of 36% in chromosome tests. After quality control, ultrasound physicians measure NT more accurately, but differences among measurements remain. Measurements by experienced ultrasound physicians are closer to expected values, usually lower than expected. Monitoring fetal NT and CRL measurements helps improve measurement accuracy. Increasing structural screening during NT examinations, especially for the fetal heart, enhances the detection rate of chromosomal abnormalities.

Chromosomal Microarray Analysis in Fetuses with Ultrasound Abnormalities.

To explore and evaluate the value of chromosomal microarray analysis (CMA) in prenatal diagnosis of fetuses with ultrasound abnormalities. A retrospective analysis was performed on 370 fetuses with ultrasound abnormalities received invasive prenatal diagnosis at Meizhou People's Hospital from October 2022 to December 2023. Fetal specimens were analyzed by CMA, and the detection rates of aneuploidy and pathogenic (P)/likely pathogenic (LP) copy number variations (CNVs) in ultrasound structural abnormalities (malformations of fetal anatomy) and non-structural abnormalities (abnormalities of fetal nonanatomical structure) were analyzed. There were 114 (30.8%) cases with isolated ultrasound structural abnormalities, 226 (61.1%) cases with isolated non-structural abnormalities (182 isolated ultrasound soft markers abnormalities, 30 isolated fetal growth restriction (FGR), and 8 isolated abnormalities of amniotic fluid volume), and 30 (8.1%) cases with both structural and non-structural abnormalities. The overall detection rate of aneuploidy and P/LP CNVs in isolated ultrasonic structural abnormalities was 5.3%, among which cardiovascular system abnormalities were the highest. In addition, the largest number of fetuses with non-structural abnormalities was nuchal translucency (NT) thickening (n = 81), followed by ventriculomegaly (n = 29), and nasal bone dysplasia (n = 24). The detection rate of chromosomal abnormalities of fetuses with abnormal ultrasound soft markers was 9.9%, and the detection rate in single abnormal ultrasound soft marker, and multiple ultrasound soft markers abnormalities was 9.7% (16/165) and 11.8% (2/17), respectively. Moreover, the detection rate of chromosomal abnormalities of fetuses with FGR and structural abnormalities combined with non-structural abnormalities was 6.7% (2/30), and 13.3% (4/30), respectively. The incidence of chromosomal abnormalities (aneuploidy and P/LP CNVs) varies among different fetal ultrasound abnormalities.

Prenatal evaluation of genetic variants in fetuses with small head circumference: A single-center retrospective study

Objectives: To comprehensively evaluate the contributions of numerical chromosomal abnormality, copy number variant (CNV), and sequence variant (SV) to fetuses with small head circumference in a Chinese cohort using chromosome microarray analysis and whole exome sequencing. Methods: A total of 157 fetuses with small heads defined as head circumference < − 2 standard deviation (SD) were recruited between October 2014 and March 2023. We used the ultrasonic measurement parameter Z-score to define small head as possible microcephaly (3 < Z ≤ -2), microcephaly (-5 < Z ≤ -3), or pathologic microcephaly (Z ≤ -5). Ultrasound findings and genetic results were analyzed. Results: The overall diagnostic yield of chromosomal abnormalities by microarray analysis was 13 %. Whole exome sequencing revealed eight novel variants and two interesting candidate genes and provided a 25.4 % incremental yield compared with microarray analysis. Of the detected SVs, 56 % were de novo and the most common inheritance pattern was autosomal dominant inheritance presented in 11/16 fetuses. Compared with isolated small heads, non-isolated small heads had a significantly higher detection rate of chromosomal abnormalities (16 % vs. 3.0 %, P = 0.049) but not SVs (24 % vs. 5.5 %, P = 0.126). Subgroup analysis showed that intracranial anomalies had a similar high detection rate of SVs in fetuses with all small heads subgroups while no chromosomal abnormalities and causative SVs were found in fetuses with isolated possible microcephaly. Conclusions: Ultrasound findings of small fetal head circumference < 3 SD below the mean, especially those with intracranial structural abnormalities, indicate the need for genetic counseling. Genetic variants, mainly copy number variants and SV, may be responsible for the substantial proportion of small fetal head circumference, while most are de novo. Whole exome sequencing and microarray analysis are effective diagnostic approaches for this population.

Chromosomal Abnormalities in Early Pregnancy Losses: A Study of 900 Samples.

Chromosomal abnormalities are the most common causes of early pregnancy losses (EPLs). In this study, we aimed to evaluate the incidence and spectrum of chromosomal abnormalities in EPLs and correlate them with different clinical characteristics. We performed Quantitative Fluorescent PCR (QF-PCR), followed by subtelomeric Multiplex Ligation Probe Amplification (MLPA) analysis to detect chromosomal abnormalities in 900 products of conceptions (POCs) from EPLs collected over a period of 10 years. Chromosomal abnormalities were present in 56.25% of uncontaminated EPLs, with significantly higher incidence in women ≥36 years (71.37%, p<0.0001) in comparison to women ≤30 years of age (43.40%). Trisomies were also more common in women ≥36 years (79.68%, p<0.0001) than in those ≤30 years of age (48.70%). In contrast, triploidy and monosomies were more prevalent in women ≤30 years of age (26.09%, p<0.0001 and 16.52%, p=0.0066 respectively) than in women ≥36 years of age (6.42% and 6.42% respectively). Trisomy 16 was more common in women ≤30 (39.29%, p=0.0009) than in those ≥36 years of age (16.78%), while trisomy 22 was predominant among women ≥36 (23.49%, p=0.013), and was not present in the group of women ≤30 years of age. The frequency of chromosomal abnormalities in POCs from women with sporadic (61.19%) was higher than in those with recurrent EPLs (55.21%). This difference, however, was not statistically significant (p=0.164). Although some differences in the chromosomal aneuploidy rates among women with different ABO blood groups, as well as among 6-8 and 9-11 gestational week EPLs were observed, further larger studies are required to confirm these findings. In conclusion, our study enriches the knowledge about chromosomal abnormalities as a cause of EPLs and confirms the higher incidence of foetal chromosomal abnormalities in EPLs in women of older reproductive age. Furthermore, it shows that using QF-PCR and MLPA methodologies, a high detection rate of chromosomal abnormalities in EPLs can be reached.

Prenatal diagnosis and genetic etiology analysis of talipes equinovarus by chromosomal microarray analysis

BackgroundWith the advancement of molecular technology, fetal talipes equinovarus (TE) is believed to be not only associated with chromosome aneuploidy, but also related to chromosomal microdeletion and microduplication. The study aimed to explore the molecular etiology of fetal TE and provide more information for the clinical screening and genetic counseling of TE by Chromosomal Microarray Analysis (CMA).MethodsThis retrospectively study included 131 fetuses with TE identified by ultrasonography. Conventional karyotyping and SNP array analysis were performed for all the subjects. They were divided into isolated TE group (n = 55) and complex group (n = 76) according to structural anomalies.ResultsAmong the total of 131 fetuses, karyotype analysis found 12(9.2%) abnormal results, while SNP array found 27 (20.6%) cases. Trisomy 18 was detected most frequently among abnormal karyotypes. The detection rate of SNP array was significantly higher than that of traditional chromosome karyotype analysis (P < 0.05). SNP array detected 15 (11.5%) cases of submicroscopic abnormalities that karyotype analysis did not find. The most common CNV was the 22q11.2 microdeletion. For both analyses, the overall detection rates were significantly higher in the complex TE group than in the isolated TE group (karyotype: P < 0.05; SNP array: P < 0.05). The incremental yield of chromosomal abnormalities in fetuses with unilateral TE (22.0%) was higher than in fetuses with bilateral TE (19.8%), but this difference was not statistically significant (P > 0.05). Abnormal chromosomes were most frequently detected in fetuses with TE plus cardiovascular system abnormalities.ConclusionFetal TE is related to chromosomal microdeletion or microduplication. Prenatal diagnosis is recommended for fetuses with TE, and CMA testing is preferred. CMA can improve the detection rate of chromosomal abnormalities associated with fetal TE, especially in pregnancies with complex TE.

A Novel System for the Detection of Spontaneous Abortion-Causing Aneuploidy and Its Erroneous Chromosome Origins through the Combination of Low-Pass Copy Number Variation Sequencing and NGS-Based STR Tests

During the period of 2018-2020, we first combined reported low-pass whole genome sequencing and NGS-based STR tests for miscarriage samples analysis. Compared with G-banding karyotyping, the system increased the detection rate of chromosomal abnormalities in miscarriage samples to 56.4% in 500 unexplained recurrent spontaneous abortions. In this study, a total of 386 STR loci were developed on twenty-two autosomes and two sex chromosomes (X and Y chromosomes), which can help to distinguish triploidy, uniparental diploidy and maternal cell contamination and can trace the parental origin of erroneous chromosomes. It is not possible to accomplish this with existing methods of detection in miscarriage samples. Among the tested aneuploid errors, the most frequently detected error was trisomy (33.4% in total and 59.9% in the error chromosome group). In the trisomy samples, 94.7% extra chromosomes were of maternal origin and 5.31% were of paternal origin. This novel system improves the genetic analysis method of miscarriage samples and provides more reference information for clinical pregnancy guidance.

Comparison of detection rates of chromosome G-banding karyotype analysis and fluorescence in situ hybridization among children with sex chromosome mosaicisms

To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms. A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children's Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared. The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P > 0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P < 0.05). No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.

Assessment of Combined Karyotype Analysis and Chromosome Microarray Analysis in Prenatal Diagnosis: A Cohort Study of 3710 Pregnancies.

The current study aimed to compare the characteristics of chromosome abnormalities detected by conventional G-banding karyotyping, chromosome microarray analysis (CMA), or fluorescence in situ hybridization (FISH)/CNVplex analysis and further explore the application value of combined karyotype analysis and CMA in prenatal diagnosis with a larger sample size. From March 2019 to March 2021, 3710 amniocentesis samples were retrospectively collected from women who accepted prenatal diagnosis at 16 to 22 + 6 weeks of pregnancy. The pregnant women underwent karyotype analysis and CMA. In the case of fetal chromosomal mosaicism, FISH or CNVplex analysis was utilized for validation. In total, 3710 G-banding karyotype results and CMA results from invasive prenatal diagnosis were collected. Of these, 201 (5.41%) fetuses with an abnormal karyotype were observed. The CMA analysis showed that the abnormality rate was 9.14% (340/3710). The detection rate of CMA combined with karyotype analysis was 0.35% higher than that of CMA alone and 4.08% higher than that of karyotyping alone. Additionally, 12 cases had abnormal karyotype analysis, despite normal CMA results. To further detect the chromosome mosaicism, we used FISH analysis to correct the karyotype results of case 1. Correspondingly, a total of 157 cases showed abnormal CMA results but normal karyotype analysis. We also found chromosomal mosaicism in 4 cases using CMA. Moreover, CNVplex and CMA demonstrated that representative case 15 was mosaicism for trisomy 2. Conventional G-banding karyotyping and CMA have their own advantages and limitations. A combination of karyotype analysis and CMA can increase the detection rate of chromosome abnormalities and make up for the limitation of signal detection.

Prenatal diagnosis with chromosome microarray and pregnancy outcomes of fetuses with biliary tract system abnormalities

To investigate the prenatal diagnostic value of chromosome microarray analysis (CMA) in fetuses presenting with ultrasound-based biliary tract system (BTS) anomalies. Amniocentesis was performed and CMA was applied in 271 pregnant women carrying fetuses with BTS abnormalities between April 2015 and December 2020. Pregnancy outcomes and fetal prognosis were followed from 1 to 6years. Sixteen cases (5.9%, 16/271) of chromosomal anomalies were detected. The detection rate of chromosomal abnormalities was significantly higher for fetuses with nonisolated BTS anomalies than for those with isolated BTS anomalies (9.0% vs. 0%, p=0.0017). Follow-up results were obtained from 267 fetuses, including 25 cases of termination of pregnancy (9.4%), 237 live births (88.8%), and 5 (1.9%) neonatal demises. The incidence of congenital biliary atresia in the small gallbladder and nonvisualized gallbladder groups was 3.0% (1/33) and 9.5% (7/74), respectively; however, none was detected on postnatal ultrasound reexamination in the gallbladder enlargement or the other BTS groups. An isolated BTS abnormality is not an indication for invasive prenatal chromosomal analysis. When combined with other ultrasonographic abnormalities, prenatal CMA should be provided. When a small or nonvisualized gallbladder is found prenatally, ultrasonography is limited in the differential diagnosis of congenital biliary atresia.

Comprehensive genetic analysis in first or second trimester pregnancy loss using chromosomal microarray with single nucleotide polymorphism probes

To explore possible genetic causes associated with early pregnancy loss using chromosomal microarray analysis (CMA) with single nucleotide polymorphism (SNP) probes. A retrospective review was performed by the CMA of samples from 961 patients who spontaneously aborted in our hospital before the 20th week of pregnancy. (1) The total chromosome abnormality rate in miscarriage samples was 54.44% (515/946), including single chromosome abnormality (39.53%), two chromosome abnormality (2.22%), multi-chromosome abnormality (0.42%), triploidy or hypertriploidy (4.86%), copy number variants (CNVs) in 41 cases (4.33%), regions of homozygosity (ROH, 0.74%), mosaic (2.22%) and chimera (0.11%). (2) CNV analysis of 41 cases showed that 85.36% were pathogenic and likely pathogenic, 12.20% were classified as clinical significance unknown and 2.44% were interpreted as likely benign; (3) Among the cases of ROH, 2 cases shown whole-genome homozygosity and 1 case had completely homozygous at chromosome 21. The homozygous regions in 2 cases were located at the end of the short arm of chromosome 16, suggesting the mechanism of ROH in such cases could be the result of isodisomy. Chromosome abnormality is an important genetic factor causing pregnancy loss. The application of CMA with SNP probes can indeed improve the detection rate of chromosome abnormalities and evaluate the risk of reproductive fertility in patients with pregnancy loss.

Spectrum of Chromosomal Abnormalities Detected by Conventional Cytogenetic Analysis Following Invasive Prenatal Testing of Fetuses with Abnormal Ultrasound Scans.

The frequent association between malformations and chromosomal abnormalities is now well-established. This study looks at the incidence and type of chromosomal abnormalities detected by conventional cytogenetic analysis in women undergoing invasive tests following detection of fetal anomalies on antenatal scans as well as incidence of other genetic abnormalities detected by DNA analysis of fetuses with congenital anomalies that had a normal karyotype. A retrospective, observational study of pregnant women undergoing invasive testing following identification of fetal anomalies by ultrasonography was carried out in a tertiary care facility, Vellore, India, between 2011 and 2018. 169 women underwent an invasive diagnostic procedure following detection of fetal anomalies. The most common indication for doing fetal karyotype was the presence of major fetal structural anomalies (142/169, 84%) with over a third (48/142, 34%) having multisystem involvement. Fetal hydrops was the next most common indication, detected in 18/169 (10%) fetuses. Aneuploidy was seen 19 of 25 fetuses (76%) with an abnormal karyotype with autosomal aneuploidy accounting for 13 (68%) and sex chromosome aneuploidy for seven (37%) of the fetuses. One fetus had double aneuploidy. In fetuses with normal karyotype, no additional information was obtained from further genetic testing. The overall detection rate of chromosomal abnormalities in our study using conventional cytogenetic analysis was 14.8%, the majority (72%) being associated with structural malformations, 20% with non-immune hydrops and 4% with soft markers. Abnormal karyotypes were seen in 12.7% of fetuses with structural malformations.

Application of Combined Ultrasound and Maternal Serum Biochemical Indexes in the Detection of Fetal Structural Abnormalities and Chromosomal Abnormalities

By exploring different prenatal diagnosis indications of fetal chromosomal abnormalities, it can provide a theoretical basis and reference value for clinical consultation of pregnant women with similar high-risk factors. In this paper, 1800 pregnant women undergoing amniotic fluid aspiration chromosomal examination in the prenatal diagnosis center were selected as the object of this study. Amniocentesis, fetal cell culture, and karyotype analysis were performed on pregnant women who were 14-20 weeks pregnant and had signed an informed consent. After amniocentesis fetal chromosome analysis, the type of fetal chromosomal abnormality was determined, and the detection rate of chromosomal abnormality was statistically described. Chi-square test was used for comparison between groups, P &lt; 0.05. This study shows that the use of ultrasound screening combined with maternal serum indicators is effective in screening fetal structural abnormalities and chromosomal abnormalities in early pregnancy, and significantly improves the detection rate of chromosomal abnormalities. The detection of fetal structural malformations is also very high, but it should be combined with ultrasound screening of mid-to-late pregnancy. The tricuspid regurgitation and umbilical vein a-wave reversal in the soft ultrasound index can be used as predictors of fetal congenital heart disease in early pregnancy.

Prenatal diagnosis of 913 fetuses samples using copy number variation sequencing.

BackgroundThe present study aimed to explore the etiological relationship between fetal abnormalities and copy number variations (CNVs) with the aim of intervening and preventing the birth of children with birth defects in time.MethodsSamples of 913 fetuses with puncture indications were collected from January 2017 to December 2019. Karyotype analysis and CNV sequencing (CNV‐seq) testing was performed for fetuses with ultrasonic abnormalities, a high risk of Down’s syndrome and an adverse birth history. All cases were followed up.ResultsIn total, 123 cases (13.47%) had abnormal karyotypes, including 109 cases with chromosome number abnormalities and 14 cases of chromosomal structural abnormalities. Thirty‐seven (4.05%) cases with pathogenic CNVs were detected. The detection rate of pathogenicity CNVs was 12.82% for mixed indications, followed by 7.5% for an adverse birth history, 5.88% at high risk of non‐invasive prenatal testing, 5.00% with an abnormal ultrasonic marker, 1.89% at high risk of screening for Down's syndrome and 1.45% with advanced maternal age. There were 12 (1.31%) cases with microduplications and 25 (2.74%) cases with microdeletions. Trisomy 21 (39.02%), trisomy 18 (13.82%) and Turner syndrome (9.76%) were the top three chromosome abnormalities. There were 104, 746 and 63 cases in the 11–13 weeks, 14–27 weeks 28–38 weeks gestational ages, respectively. The abnormal rates of fetal chromosome aneuploidy and the rate of pathogenic CNVs were decreased and increased with the increase of gestational age (p < 0.05), respectively.ConclusionsCompared with karyotype analysis, CNV‐seq can improve the detection rate of chromosomal abnormalities. CNV‐seq combined karyotype analysis should be performed simultaneously in fetuses with puncture indications.

Application of Array-based Comparative Genomic Hybridization in Diagnostic Assessment of Abnormal Prenatal Serological Screening Results of Down's Syndrome

To explore the application of array-based comparative genomic hybridization (a-CGH) technology in the prenatal diagnostic assessment of abnormal serological prenatal screening results of Down's syndrome (DS). A total of 3 578 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal serological prenatal screening results were selected. The samples were categorized into 3 groups, 2 624 in the high-risk group, 662 in the borderline-risk group, and 292 in the abnormal multiple of median (MoM) group. a-CGH was performed on the Agilent CGX ™ (8×60K) platform and the data were analyzed by the Genoglyphix ® software. The overall detection rate of chromosomal abnormalities was 3.38% (121/3 578). Among the chromosomal abnormalities, 49.59% (60/121) was aneuploidies, 42.15% (51/121) was pathogenic copy number variants (pCNVs), and 8.26% (10/121) was likely pathogenic CNVs (lpCNVs). The detection rate of copy number variant of uncertain significance (VUS) was 1.03% (37/3 578). In the high-risk, the borderline-risk and the abnormal MoM groups, the detection rate of chromosomal abnormalities was 3.54% (93/2 624), 2.87% (19/662) and 3.08% (9/292), respectively; the detection rate of p/lp CNVs was 1.64% (43/2 624), 1.81% (12/662) and 2.05% (6/292), respectively; the detection rate of trisomy 21 and trisomy 18 was 1.37% (36/2 624), 0.76% (5/662) and 0.34% (1/292) in the three groups, respectively. There were no significant differences in all the detection rate among these groups ( P>0.05). One sample with X(51)/XYY(49) confirmed by fluorescence in situ hybridization (FISH) was misdiagnosed by a-CGH. Prenatal diagnosis with a-CGH is of great significance for reducing birth defects in pregnancies with abnormal serological prenatal screening results of DS. It can also be used to detect CNVs of microdeletion/microduplication syndromes.

Application of the BACs-on-Beads assay for the prenatal diagnosis of chromosomal abnormalities in Quanzhou, China

BackgroundAn increasing number of techniques have been used for prenatal diagnosis of genetic abnormalities. Our initial objective was to explore the value of the BACs-on-Beads (BoBs) assay for the prenatal diagnosis of aneuploidies and microdeletion/microduplication syndromes in Quanzhou, Southeast China.MethodsA total of 1409 pregnant women with high-risk factors for chromosomal abnormalities admitted to Quanzhou Women’s and Children’s Hospital were enrolled in this study. BoBs assays and karyotype analyses were conducted for all subjects. Subsequently, chromosome microarray analysis (CMA) or fluorescence in situ hybridization (FISH) was performed to validate the findings.ResultsIn this study, karyotype analysis and BoBs assay failed in 4 cases, and 2 cases, respectively. A total of 1403 cases were successfully analyzed, with success rates of 99.72% (1405/1409) and 99.85% (1407/1409) for karyotype analysis and Bobs assay, respectively. BoBs assay rapidly detected chromosomal aneuploidies in line with the karyotyping data. Additionally, 23 cases of microdeletions/microduplications were detected by BoBs assay but missed by karyotyping, including 22q11.2 microdeletions/microduplications, 5p15.32p15.33 microdeletion, Xp22.31 microdeletions/microduplications, Xq27.3 microdeletion, and Yp11.2 and Yq11.22q11.222 microduplication. In comparison with karyotyping, fewer mosaicisms were identified by BoBs assay. A high detection rate of chromosomal abnormalities was observed in the high-risk group during noninvasive prenatal testing (NIPT) (41.72%) and the abnormal ultrasound group (13.43%).ConclusionsBoBs assay can be used for the rapid and efficient prenatal diagnosis of common aneuploidies and microdeletion/microduplication syndromes. Moreover, the combined use of BoBs assay and karyotyping in prenatal diagnosis may allow for a more effective detection of chromosomal abnormalities.

Evaluation of chromosomal abnormalities and copy number variations in fetuses with ultrasonic soft markers

BackgroundSome ultrasonic soft markers can be found during ultrasound examination. However, the etiology of the fetuses with ultrasonic soft markers is still unknown. This study aimed to evaluate the genetic etiology and clinical value of chromosomal abnormalities and copy number variations (CNVs) in fetuses with ultrasonic soft markers.MethodsAmong 1131 fetuses, 729 had single ultrasonic soft marker, 322 had two ultrasonic soft markers, and 80 had three or more ultrasonic soft markers. All fetuses underwent conventional karyotyping, followed by single nucleotide polymorphism (SNP) array analysis.ResultsAmong 1131 fetuses with ultrasonic soft markers, 46 had chromosomal abnormalities. In addition to the 46 fetuses with chromosomal abnormalities consistent with the results of the karyotyping analysis, the SNP array identified additional 6.1% (69/1131) abnormal CNVs. The rate of abnormal CNVs in fetuses with ultrasonic soft marker, two ultrasonic soft markers, three or more ultrasonic soft markers were 6.2%, 6.2%, and 5.0%, respectively. No significant difference was found in the rate of abnormal CNVs among the groups.ConclusionsGenetic abnormalities affect obstetrical outcomes. The SNP array can fully complement conventional karyotyping in fetuses with ultrasonic soft markers, improve detection rate of chromosomal abnormalities, and affect pregnancy outcomes.