Prenatal diagnosis of 18p deletion and 8p trisomy syndrome: literature review and report of a novel case.

18p deletion syndrome constitutes one of the most frequent autosomal terminal deletion syndromes, affecting one in 50,000 live births. The syndrome has un-specific clinical features which vary significantly between patients and may overlap with other genetic conditions. Its prenatal description is extremely rare as the fetal phenotype is often not present during pregnancy. Trisomy 8p Syndrome is characterized by heterogenous phenotype, with the most frequent components to be cardiac malformation, developmental and intellectual delay. Its prenatal diagnosis is very rare due to the unspecific sonographic features of the affected fetuses. We present a very rare case of a fetus with multiple anomalies diagnosed during the second trimester whose genomic analysis revealed a 18p Deletion and 8p trisomy Syndrome. This is the first case where this combination of DNA mutations has been described prenatally and the second case in general. The presentation of this case, as well as the detailed review of all described cases, aim to expand the existing knowledge regarding this rare condition facilitating its diagnosis in the future.

A rapid PCR-free next-generation sequencing method for comprehensive diagnosis of chromosome disease syndromes in prenatal samples.

The aim of this study is to investigate the application performance of rapid copy number variation sequencing (rCNV-seq) technology for the detection of chromosomal abnormalities during prenatal diagnosis. Samples were collected from 424 pregnant women who were at high-risk for noninvasive prenatal screening in Kunming Maternal and Child Care Hospital from January 2018 to May 2022. rCNV-seq technique was used to detect fetal chromosome abnormalities and compare the results with that of chromosomal karyotype analysis. The Result showed that 330 (77.83%, 330/424) cases indicated chromosomal abnormalities among 424 high-risk pregnant women who underwent rCNV-seq. Moreover, 94 (22.17%, 94/424) cases were discovered to have copy number variations. Among the 330 fetuses with chromosomal abnormalities, common autosomal aneuploidy was observed in 203 cases (47.87%, 203/424) and sex chromosome aneuploidy was observed in 91 cases (21.46%, 91/424). Moreover, the abnormalities in multiple chromosomes were discovered in 33 cases (7.78%, 33/424), and the rare autosomal aneuploidy was observed in 3 cases (0.71%, 3/424). There were 63 fetuses (14.86%, 63/424) with pathogenic CNVs among the 94 fetuses with variable copy numbers. Of the 245 pregnant women who voluntarily selected G-band karyotyping, 1 fetus with copy number variation had normal karyotype results, and the remaining women were consistent with rCNV-seq. Our study revealed that rCNV-seq has higher accuracy in detecting common trisomy and can also detect chromosomal microdeletions or microduplications that cannot be detected by G-banding karyotype analysis. There is no effective treatment for chromosomal diseases, so it is particularly important to prevent chromosomal diseases through genetic counseling and prenatal diagnosis of chromosomal diseases.

Antenatal description of large 4q13.2q21.23 deletion and outcomes.

BACKGROUND: 4q21 microdeletion syndrome is an emergent non-recurrent genomic disorder characterized by facial dysmorphy, progressive growth retardation, severe intellectual deficit, and absent or severely delayed speech. Deletions occur in clusters along 4q interstitial or terminal regions. 4q chromosomal aberrations are variable in type, size, and breakpoint. Genotype-phenotype correlation is a challenging task. The recurrent antenatal feature associated a posteriori with this syndrome is intrauterine growth retardation. There are very few precise antenatal descriptions of this syndrome. METHODS: We report here the first antenatal history of one of the largest deletion of this region. RESULTS: Our case harbored a 16.9 Mb deletion encompassing 135 protein coding genes including 20 OMIM morbid genes involved in neurological and cognitive abilities. Those breakpoints overlap two clusters of described microdeletion syndromes of cytogenetic band 4q13 and 4q21. CONCLUSION: From the end of the second trimester, set of call signs associated with this syndrome can be completed by: excess of amniotic fluid, mild growth retardation, short long bones, bony anomalies of the extremities, and bulging cheeks. So, emphasis should be placed on the examination of the extremities, and the face during the routine targeted prenatal ultrasound.

Clinically significant findings in a decade-long retrospective study of prenatal chromosomal microarray testing.

BACKGROUND: Chromosomal microarray (CMA) is commonly utilized in the obstetrics setting. CMA is recommended when one or more fetal structural abnormalities is identified. CMA is also commonly used to determine genetic etiologies for miscarriages, fetal demise, and confirming positive prenatal cell-free DNA screening results. METHODS: In this study, we retrospectively examined 523 prenatal and 319 products-of-conception (POC) CMA cases tested at Nationwide Children's Hospital from 2011 to 2020. We reviewed the referral indications, the diagnostic yield, and the reported copy number variants (CNV) findings. RESULTS: In our cohort, the diagnostic yield of clinically significant CNV findings for prenatal testing was 7.8% (n = 41/523) compared to POC testing (16.3%, n = 52/319). Abnormal ultrasound findings were the most common indication present in 81% of prenatal samples. Intrauterine fetal demise was the common indication identified in POC samples. The most common pathogenic finding observed in all samples was isolated trisomy 21, detected in seven samples. CONCLUSION: Our CMA study supports the clinical utility of prenatal CMA for clinical management and identifying genetic etiology in POC arrays. In addition, it provides insight to the spectrum of prenatal and POC CMA results as detected in an academic hospital clinical laboratory setting that serves as a reference laboratory.

Intrauterine ultrasound phenotyping, molecular characteristics, and postnatal follow-up of fetuses with the 15q11.2 BP1-BP2 microdeletion syndrome: a single-center, retrospective clinical study.

OBJECTIVES: The 15q11.2 BP1-BP2 microdeletion is associated with neurodevelopmental diseases. However, most studies on this microdeletion have focused on adults and children. Thus, in this study, we summarized the molecular characteristics of fetuses with the 15q11.2 BP1-BP2 microdeletion and their postnatal follow-up to guide prenatal diagnosis. METHODS: Ten thousand fetuses were retrospectively subjected to karyotype analysis and chromosome microarray analysis. RESULTS: Chromosome microarray analysis revealed that 37 (0.4%) of the 10,000 fetuses had 15q11.2 BP1-BP2 microdeletions. The fragment size of the 15q11.2 BP1-BP2 region was approximately 312-855 kb and encompassed TUBGCP5, CYFIP1, NIPA2, and NIPA1 genes. Twenty-five of the 37 fetuses with this microdeletion showed phenotypic abnormalities. The most common ultrasonic structural abnormality was congenital heart disease, followed by renal dysplasia and Dandy-Walker malformation. The 15q11.2 BP1-BP2 microdeletion was inherited from the father and mother in 6 and 10 cases, respectively, and de novo inherited in 4 cases. In the postnatal follow-up, 16.1% of the children had postnatal abnormalities. CONCLUSION: Fetuses with the 15q11.2 BP1-BP2 microdeletion showed high proportions of phenotypic abnormalities, but the specificity of penetrance was low. Thus, fetuses with this syndrome are potentially at a higher risk of postnatal growth/behavioral problems and require continuous monitoring of growth and development.

Maternal age and the risk of fetal aneuploidy: A nationwide cohort study of more than 500 000 singleton pregnancies in Denmark from 2008 to 2017.

INTRODUCTION: In this register-based study of pregnancies in Denmark, we assessed the associations between maternal age and the risk of fetal aneuploidies (trisomy 21, trisomy 18, trisomy 13, triploidy, monosomy X and other sex chromosome aberrations). Additionally, we aimed to disentangle the maternal age-related effect on fetal aneuploidies by cases with translocation trisomies and mosaicisms. MATERIAL AND METHODS: We followed a nationwide cohort of 542 375 singleton-pregnant women attending first trimester screening in Denmark between 2008 and 2017 until delivery, miscarriage or termination of pregnancy. We used six maternal age categories and retrieved information on genetically confirmed aneuploidies of the fetus and infant from the national cytogenetic register. RESULTS: We confirmed the known associations between advanced maternal age and higher risk of trisomy 21, 18, 13 and other sex chromosome aberrations, especially in women aged ≥35 years, whereas we found no age-related associations with triploidy or monosomy X. Cases with translocation trisomies and mosaicisms did not influence the overall reported association between maternal age and aneuploidies. CONCLUSION: This study provides insight into the accurate risk of fetal aneuploidies that pregnant women of advanced ages encounter.

Artificial intelligence for prenatal chromosome analysis.

This review article delves into the rapidly advancing domain of prenatal diagnostics, with a primary focus on the detection and management of chromosomal abnormalities such as trisomy 13 ("Patau syndrome)", "trisomy 18 (Edwards syndrome)", and "trisomy 21 (Down syndrome)". The objective of the study is to examine the utilization and effectiveness of novel computational methodologies, such as "machine learning (ML)", "deep learning (DL)", and data analysis, in enhancing the detection rates and accuracy of these prenatal conditions. The contribution of the article lies in its comprehensive examination of advancements in "Non-Invasive Prenatal Testing (NIPT)", prenatal screening, genomics, and medical imaging. It highlights the potential of these techniques for prenatal diagnosis and the contributions of ML and DL to these advancements. It highlights the application of ensemble models and transfer learning to improving model performance, especially with limited datasets. This also delves into optimal feature selection and fusion of high-dimensional features, underscoring the need for future research in these areas. The review finds that ML and DL have substantially improved the detection and management of prenatal conditions, despite limitations such as small sample sizes and issues related to model generalizability. It recognizes the promising results achieved through the use of ensemble models and transfer learning in prenatal diagnostics. The review also notes the increased importance of feature selection and high-dimensional feature fusion in the development and training of predictive models. The findings underline the crucial role of AI and machine learning techniques in early detection and improved therapeutic strategies in prenatal diagnostics, highlighting a pressing need for further research in this area.

A Retrospective Analysis of Robertsonian Translocations from a Single Center in China.

Robertsonian translocations (ROBs) are the most common structural chromosomal abnormalities in the general population, with an estimated incidence rate of 1/1000 births. In this study, we retrospectively analyzed the cases of ROBs from September 2015 to August 2022 and totally identified ROB carriers from 84,569 specimens karyotyped in a single accredited laboratory in China, including 189 cases of balanced ROBs and 3 of mosaic ROBs. Microsoft Excel and descriptive statistics were used to record and analyze the collected data. The male/female ratio of ROBs is 1/1.29, with der(13;14) and der(14;21) being the main karyotypes. Among the 192 patients, 7 were lost to follow-up, 82 had given birth, and 103 were childless (such as miscarriage, fetal chromosomal abnormalities, in vitro fertilization (IVF) failure, or divorce). A total of 44 amniocenteses were performed in 42 couples; ROB cases with natural pregnancies showed that the normal karyotype and balanced ROBs of fetal accounted for 66.67% (16/24), while the results of assisted pregnancies showed 90.00% (18/20). This study represents the largest collections of ROBs in Jiangxi population and reminder that the ROB carriers can achieve the ideal outcome for pregnancy with the appropriate genetic guidance and assisted reproductive technologies (ART).

High-resolution PGT-A results in incidental identification of patients with small pathogenic copy number variants.

PURPOSE: This study aimed to evaluate whether a high-throughput high-resolution PGT-A method can detect copy number variants (CNVs) that could have clinical implications for patients and their embryos. METHODS: A prospective analysis of PGT-A cases was conducted using a high-resolution SNP microarray platform with over 820,000 probes. Cases where multiple embryos possessed the same segmental imbalance were identified, and preliminary PGT-A reports were issued recommending either parental microarray or conventional karyotyping to identify CNVs or translocations. RESULTS: Analysis of 6080 sequential PGT-A cases led to identification of 41 cases in which incidental findings were observed (0.7%) and parental testing was recommended. All cases, in which parental studies were completed, confirmed the original PGT-A incidental findings. In 2 of the cases, parental studies indicated a pathogenic variant with clinical implications for the associated embryos. In one of these cases, the patient was identified as a carrier of a duplication in chromosome 15q11.2:q11.2 (SNRPN + +), which is associated with autism spectrum disorder. In the second case, the patient was heterozygous positive for an interstitial deletion of 3p26.1:p26.3, which is associated with 3p deletion syndrome and had clinical implications for the patient and associated embryos. In each case, parental studies were concordant with PGT-A findings and revealed the presence of an otherwise unknown CNV. CONCLUSION: High-throughput high-resolution SNP array-based PGT-A has the ability to detect previously unknown and clinically significant parental deletions, duplications, and translocations. The use of cost-effective SNP array-based PGT-A methods may improve the effectiveness of PGT by identifying and preventing previously unknown pathogenic CNVs in children born to patients seeking in vitro fertilization.

Identifying a failure-to-thrive fraternal twin profile with 3q29 deletion syndrome.

In 2005, the 3q29 deletion syndrome was identified and defined as a rare chromosomal anomaly that effects approximately one in 30,000-40,000 children. It has a complex neuropsychiatric profile, often resulting in developmental delays, intellectual disabilities, attentional deficits, classic physical traits, and behavioral health disturbances, including social and emotional issues. Rarely has this syndrome been seen and evaluated in fraternal twins, only one of whom has the 3q29 deletion syndrome. This case study highlights Twin 1's strengths and weaknesses and compares her 2020 neuropsychological data, including a comparison of her Reitan-Indiana Neuropsychological Battery (RINB) results to her 2022 profile, which reveals a failure-to-thrive profile.

Evaluation of chromosomal abnormalities in the postnatal cohort: A single-center study on 14,242 patients.

BACKGROUND AND AIM: Chromosomal analysis is a laboratory technique used to examine the chromosomes of an individual, offering insights into chromosome numbers, structures, and arrangements to diagnose and comprehend genetic diseases. This retrospective study provides a comprehensive understanding of the distribution by indications in a large cohort of 14,242 patients and the frequency of chromosomal abnormalities in different clinical populations. METHOD: The study examined various indications for karyotype evaluation, with recurrent pregnancy loss being the most common indication, followed by intellectual disability, dysmorphic features, congenital anomalies, and developmental delay. RESULTS: The overall chromosomal abnormality rate was found to be 5.4%, with numerical abnormalities accounting for the majority of cases (61.7%). Trisomies, particularly trisomy 21, were the most frequent numerical abnormalities. In terms of structural abnormalities, inversions and translocations were the most commonly identified. The rates of chromosomal anomalies varied in specific indications such as amenorrhea, disorders of sex development, and Turner syndrome. The study also highlighted significant differences between males and females in the presence of chromosomal abnormalities across certain indications. Males exhibited a higher incidence of chromosomal abnormalities in cases of Down syndrome and infertility, whereas females showed higher abnormalities in terms of recurrent pregnancy loss. CONCLUSION: While this study provides valuable insights into the frequency and distribution of chromosomal abnormalities, it has limitations, including its retrospective design and reliance on data from a single medical genetics department. Nevertheless, the findings emphasize the importance of karyotype analysis in diagnosing chromosomal disorders and providing appropriate management, while also pointing to potential gender-related variations in chromosomal abnormalities that warrant further investigation.

Indications, types, and diagnostic implications of prenatal genetic testing in Sub-Saharan Africa: A descriptive study.

OBJECTIVE: To describe indications, test types, and results of prenatal diagnostic genetic amniocentesis among Ethiopian pregnant women. METHODS: This study was a descriptive study on prenatal diagnostic genetic testing among Ethiopian pregnant women with certain indications and it was conducted at St. Paul's Hospital Millennium Medical College (Addis Ababa, Ethiopia) from January 2017 to April 2023. Data on sociodemographic characteristics, genetic testing indications, types, and results were collected electronically. Data were analysed using SPSS version 23. RESULTS: A total of 159 cases were analysed. The commonest indication for genetic testing among the study subjects was major fetal structural anomalies identified on specialized prenatal anatomic scanning of the index pregnancy detected in 71(44.7%) cases. Down syndrome and Edward syndrome were the commonest genetic aberrations detected accounting for 6.3% (10/159) and 4.4% (7/159), respectively. Among the rare genetic aberration detected were Di-George syndrome (0.6%) and Duchenne muscular dystrophy (0.6%). CONCLUSION: Findings of our study underscore the importance of diagnostic prenatal testing in a Sub-Saharan Africa setting, as common (trisomy 21&18) and rare genetic defects were identified using this important prenatal diagnostic testing. Considering the implications of detecting chromosomal abnormalities for future counselling and care, carrier state in parents for some chromosomal anomalies, and planning post-natal management of some abnormalities that are associated with aneuploidies (notably cardiac anomalies), initiation of diagnostic prenatal genetic testing service at tertiary public health facilities should be acted up on.

Age of diagnosis for children with chromosome 15q syndromes.

OBJECTIVE: The objective of this study was to identify the age of diagnosis for children with one of three neurogenetic conditions resulting from changes in chromosome 15 (Angelman syndrome [AS], Prader-Willi syndrome [PWS], and duplication 15q syndrome [Dup15q]). METHODS: Data about the diagnostic process for each condition were contributed by the advocacy organizations. Median and interquartile ranges were calculated for each condition by molecular subtype and year. Comparison tests were run to explore group differences. RESULTS: The median age of diagnosis was 1.8 years for both AS and Dup15q. PWS was diagnosed significantly younger at a median age of 1 month. Deletion subtypes for both PWS and AS were diagnosed earlier than nondeletion subtypes, and children with isodicentric duplications in Dup15q were diagnosed earlier than those with interstitial duplications. CONCLUSION: Understanding variability in the age of diagnosis for chromosome 15 disorders is an important step in reducing the diagnostic odyssey and improving access to interventions for these populations. Results from this study provide a baseline by which to evaluate efforts to reduce the age of diagnosis for individuals with these conditions.

Fetal mosaicism, should conventional karyotype always be performed?

BACKGROUND AND PURPOSE: The application of classical cytogenetic and DNA-based molecular techniques to detect cell lineages of mosaicism derived from cultured or noncultured fetal cells may result in discordant results. This retrospective study aimed to assess the inconsistent diagnostic outcomes, technical availability, and limitations of chromosomal microarray analysis (CMA) and karyotyping for mosaicism. METHODOLOGY: A total of 75 fetuses diagnosed with mosaicism by karyotype analysis or CMA were selected, and the results from both the methods were compared and further analyzed. RESULTS: A total of 42 (56%, 42/75) CMA results were consistent with karyotypes, consisting of 22 cases of mosaic sex chromosomal abnormalities, 8 routine autosomal aneuploidy cases, 8 other autosome aneuploidy cases, 3 large cryptic genomic rearrangements, and 1 small supernumerary marker chromosome. Discrepancy between karyotype analysis and CMA was observed in 33 (44%, 33/75) mosaicisms involving 15 sex chromosomal abnormalities, 1 routine autosomal aneuploidies, 5 other autosome aneuploidy cases, 8 large cryptic genomic rearrangements, and 4 small supernumerary marker chromosomes. CONCLUSION: Considering the disparities between methods as well as the cell populations analyzed, both CMA and karyotype analysis have their own advantages and disadvantages. Therefore, CMA should ideally be used in combination with karyotyping to detect more cases of mosaicism than using either test alone.

Noninvasive prenatal screening with conventional sequencing depth to screen fetal copy number variants: A retrospective study of 19 144 pregnant women.

AIM: To investigate the detectability of noninvasive prenatal screening (NIPS) with conventional sequencing depth to detect fetal copy number variants. METHODS: We performed a retrospective study in a total of 19 144 pregnant women. Their cell-free plasma DNA were assessed for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and genome-wide copy number variants by NIPS at conventional sequencing depth. RESULTS: Three hundred seventy-four cases (2.0%, 374/19 144) with abnormal results were detected, which including 84 cases (0.4%, 84/19 144) with high risk of trisomy 21, 18, and 13, 90 cases (0.5%, 90/19 144) with high risk of sex chromosome abnormalities (SCA), and 44 cases (0.2%, 44/19 144) with high risk of other chromosome aneuploidies. One hundred fifty-six cases (0.8%, 156/19 144) with high risk of copy number variations (CNVs) were also detected. In following prenatal diagnosis, composite positive predictive value (PPV) of trisomy 21, 18, and 13 was 69.6% (48/69). The PPV of SCAs was 37.3% (19/51). And the PPVs for CNVs was detected as 51.0% (<5 Mb), 71.4% (5 Mb ≤ CNV ≤10 Mb), 56.5% (>10 Mb). Finally, a follow-up about the pregnancy outcomes were conducted for all available cases. CONCLUSIONS: NIPS yielded high PPVs for trisomy 21, 18, and 13 aneuploidies and moderate PPVs for SCAs and CNVs. The screening effectiveness was closely related to the size of CNV fragments. Larger CNVs, especially larger than 5 Mb, could be detected more accurately by NIPS in our analytic technique. Meanwhile, diagnostic confirmation by microarray analysis was highly recommended.

[The value of non-invasive prenatal testing for the identification of numerical and structural chromosomal abnormalities and copy number variations in the fetuses].

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. METHODS: 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. RESULTS: Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). CONCLUSION: NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.

[Phelan-McDermid syndrome associated with a novel heterozygous mutation in the SHANK3 gene]. / Sindrom Felan­MakDermid, assotsiirovannyi s novoi geterozigotnoi mutatsiei v gene SHANK3.

Phelan-McDermid syndrome (PMS) is a hereditary disorder associated with microdeletions of chromosome 22q13 or point mutations in SHANK3, characterized by mental and speech delays, intellectual disability, epilepsy and autism spectrum disorder. We describe a case PMS associated with a heterozygous mutation c.2486delC (p.Pro829fs) in SHANK3. The diagnostic pathway of a female patient with PMS took more than 7 years; the reason for treatment was the onset of epileptic seizures and impaired speech development. The existence of different types of rearrangements and genomic variations can explain the high clinical variability observed in individuals with PMS. Only molecular diagnosis can accurately diagnose individuals with PMS for follow-up and medical genetic counselling of families.

The role of ultrasound in first-trimester screening after the introduction of NIPT as a service of public health insurance - a consensus statement of the Fetal Medicine Foundation (FMF) Germany.

Combined first-trimester screening (FTS) and noninvasive prenatal testing (NIPT) have been proven to be reliable noninvasive procedures to detect the most common chromosomal abnormalities (trisomies 21, 18, 13) in the first trimester. The aim of this paper is to demonstrate the strengths and limitations of these two procedures and to give a consensus statement of the Fetal Medicine Foundation (FMF) Germany on how to use the two techniques in the first trimester after the introduction of NIPT as a service of the statutory health insurance companies in Germany.

[Retrospective analysis of cell-free fetal DNA prenatal testing of maternal peripheral blood].

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women. METHODS: A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes. RESULTS: Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found. CONCLUSION: NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.

[The value of combined CNV-Seq and chromosomal karyotyping for the detection of amniocytic mosaicisms and a literature review].

OBJECTIVE: To assess the value of combined copy number variation sequencing (CNV-seq) and chromosomal karyotyping for the diagnosis of amniocytic mosaicisms, in addition with a literature review. METHODS: Forty cases of amniocytic mosaicisms detected at the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2021, in addition with 245 mosaicisms retrieved from 11 recent literature were evaluated in terms of detection rate, consistency rate, and pregnancy outcomes. RESULTS: The detection rate of amniocytic mosaicisms was 0.46% (40/8 621) in our center. And its consistency rate with chromosomal karyotyping was 75.0% (30/40). After genetic counseling, 30 (75.0%) couples had opted to terminate the pregnancy, 5 (12.5%) had decided to continue with the pregnancy, 3 (7.5%) fetuses were born alive, and 2 cases (5.0%) were lost in touch. By contrast, 245 cases (0.39%) of mosaicisms were identified among 63 577 amniotic samples, with a consistency rate of 62.8% (103/164) with other techniques. Among these, 114 cases (55.1%) were terminated, 75 (36.2%) were born alive, and 18 (8.7%) were lost during the follow up. CONCLUSION: Combined CNV-seq and chromosomal karyotyping has a high value for the detection of amniotic mosaicisms.