[Prenatal diagnosis of fetal microdeletion and microduplication syndromes among pregnant women with advanced maternal ages].

OBJECTIVE: To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) and/or copy number variation sequencing (CNV-seq) for the prenatal diagnosis for women with advanced maternal ages, and to explore the challenges of prenatal genetic counseling brought by the types of fetal CNVs and uncertainty of related phenotypes. METHODS: A retrospective analysis was carried out on 1 841 women with advanced maternal age who underwent interventional prenatal diagnosis at the Prenatal Diagnosis Center of Xiamen University Affiliated Women and Children's Hospital from January 2017 to December 2020. Routine chromosomal karyotyping analysis and CMA/CNV-seq detection were carried out. RESULTS: CMA/CNV-seq had detected pathogenic variants in 2 cases which had failed karyotyping analysis. Two hundred and twenty one fetal chromosomal abnormalities were detected by karyotyping analysis, among which 187 were detected by CMA/CNV-seq. CMA/CNV-seq analysis of 23 cases with balanced chromosome structural aberrations and 10 cases with low proportion mosaicisms (including a marker chromosome) had yielded a negative result. In addition, 26 cases (26/1 841, 1.4%) with pathogenic CNVs were discovered among those with a normal karyotype, of which 13 (50.0%) were recurrent CNVs associated with neurocognitive impairment, with 22q11.21 microdeletions and microduplications being the most common types (26.92%). CONCLUSION: The combination of karyotyping analysis and CMA/CNV-seq not only increased the rate of prenatal diagnosis, but also complemented with each other, which has facilitated genetic counseling and formulation of prenatal diagnosis strategy for the affected families.

[Clinical features and genetic analysis of two fetuses with ring chromosome 21 mosaicism].

OBJECTIVE: To investigate the perinatal clinical phenotype and genetic characteristics of two fetuses with ring chromosome 21 mosaicisms. METHODS: Two fetuses who were diagnosed at the Xiamen Maternal and Child Health Care Hospital in November 2021 were selected as the study subjects. Clinical data of the two fetuses were collected. Conventional G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out for the fetuses and their parents. RESULTS: Prenatal ultrasonography of fetus 1 has revealed absence of nasal bone, ventricular septal defect, persistent left superior vena cava, and mild tricuspid regurgitation. Chromosomal karyotyping was 46,X?,dic r(21;21)(p12q22;q22p12)[41]/45,X?,-21[9]. CMA has revealed a 30.00 Mb quadruplication at 21q11.2q22.3 and a 3.00 Mb deletion at 21q22.3. For fetus 2, ultrasonography has revealed pointed echo of the nasal bone. The fetus was found to have a karyotype of 46,X?,r(21)(p12q22)[83]/45,X?,-21[14]/46,X?,dic r(21;21)(p12q22;q22p12)[3]. CMA has revealed a 5.10 Mb quadruplication at 21q22.12q22.3 and a 2.30 Mb deletion at 21q22.3. CONCLUSION: The perinatal phenotype of the two fetuses with ring chromosome 21 mosaicisms is related to the duplication of chromosomal segments near the breakpoints of the chromosomal deletions. The combined chromosomal karyotyping and CMA has enabled prenatal diagnosis and genetic counseling for these families.

Fetal Tethered Spinal Cord: Diagnostic Features and Its Association with Congenital Anomalies.

OBJECTIVE: We assessed the frequency and type of associated congenital anomalies encountered with fetal tethered spinal cord (TSC) determined prenatally. METHOD: A retrospective review was conducted based on the associated fetal abnormalities following diagnosis of low-lying fetal conus medullaris during the prenatal ultrasound. RESULTS: Of the 26 fetuses with low-lying conus medullaris, four were solitary TSC and 22 had TSC combined with associated congenital malformations, including four cases with spina bifida occulta, four cases with spina bifida aperta, one case with severe hydrocephalus, and 13 cases with multisystem congenital malformations. Among all the 13 cases with combined multisystem congenital malformations, four cases had vertebral defects, anal anomalies, cardiac defects, trachea-esophageal fistula, renal anomalies, and limb anomalies (VACTERL) syndrome, two cases had combined kidney development abnormalities, one case had cloacal exstrophy (OEIS syndrome), and six cases had chromosomal abnormalities (one case of chromosome 7q deletion, two cases of trisomy 13 syndrome, one case of trisomy 18 syndrome, one case of trisomy 9 syndrome, and one case of chromosome 4p deletion). CONCLUSIONS: Low-lying conus medullaris found during prenatal ultrasound examination were often associated with neural tube malformations or multi-systemic complex developmental malformations. The frequency of chromosomal abnormalities was 23.1%.

Prenatal Genetic Diagnosis of Fetal Cystic Hygroma: A Retrospective Single-Center Study from China.

Fetal cystic hygroma (CH) is associated with poor prognosis and chromosomal anomalies. Recent studies have suggested that the genetic background of affected fetuses is essential for predicting pregnancy outcomes. However, the detection performance of different genetic approaches for the etiological diagnosis of fetal CH remains unclear. In this study, we aimed to compare the diagnostic efficiency of karyotyping and chromosomal microarray analysis (CMA) in a local fetal CH cohort, and tried to propose an optimized testing strategy that may help improve the cost-effectiveness of disease management. We reviewed all pregnancies that underwent invasive prenatal diagnosis between January 2017 and September 2021 at one of the largest prenatal diagnostic centers in Southeast China. We collected cases identified by the presence of fetal CH. Prenatal phenotypes and laboratory records of these patients were audited, collated, and analyzed. The detection rates of karyotyping and CMA were compared, and the concordance rate of these two methods was calculated. A total of 157 fetal CH cases were screened from 6,059 patients who underwent prenatal diagnosis. Diagnostic genetic variants were identified in 44.6% (70/157) of the cases. Karyotyping, CMA, and whole-exome sequencing (WES) identified pathogenic genetic variants in 63, 68, and 1 case, respectively. The Cohen's κ coefficient between karyotyping and CMA was 0.96, with a concordance of 98.0%. Of the 18 cases in which cryptic copy number variants <5 Mb were detected by CMA, 17 were interpreted as variants of uncertain significance, and the remaining cases were interpreted as pathogenic. Trio exome sequencing revealed a pathogenic homozygous splice site mutation in the PIGN gene in a case undiagnosed by CMA and karyotyping. Our study demonstrated that chromosomal aneuploidy abnormalities are the main genetic cause of fetal CH. Based on this, we recommend karyotyping combined with rapid aneuploidy detection as a first-tier approach for the genetic diagnosis of fetal CH. WES and CMA could improve the diagnostic yield when routine genetic tests fail to determine the cause of fetal CH.

Mutation Analysis of COL1A1 and COL1A2 in Fetuses with Osteogenesis Imperfecta Type II/III.

AIM: To analyze COL1A1/2 mutations in prenatal-onset OI for determine the proportion of mutations in type I collagen genes among prenatal onset OI and to provide additional data for genotype-phenotype analyses. MATERIAL AND METHODS: Ten cases of severe fetal short-limb dwarfism detected by antenatal ultrasonography were referred to our center. Before the termination of pregnancy, cordocentesis was performed for fetal karyotype and COL1A1/2 gene sequencing analysis. Postmortem radiographic examination was performed at all instances for definitive diagnosis. RESULTS: COL1A1 and COL1A2 SNP and mutations were identified in all the cases. Among these, one synonymous SNP and four synonymous SNPs were recognized in COL1A1/2, respectively, seven cases have distinct heterozygous mutations and six new COL1A1/2 gene mutations were identified. CONCLUSION: There has been substantial progress in the identification of the molecular defects responsible for skeletal dysplasias. With the constant increase in the number of identified mutations in COL1A1 and COL1A2, genotype-phenotype correlation is becoming increasingly pertinent.

[Diagnosis of a fetus with X-linked hydrocephalus due to mutation of L1CAM gene].

OBJECTIVE: To explore the genetic basis for a case of recurrent fetal congenital hydrocephalus. METHODS: Next-generation sequencing was carried out for the fetus, the gravida and two of her sisters. RESULTS: The fetus was found to harbor a c.1765T>C (p.Tyr589His) mutation in exon 14 of the L1CAM gene, which was derived from the gravida. CONCLUSION: Male fetuses with recurrent hydrocephalus should be subjected to testing of the L1CAM gene to facilitate genetic counseling and prenatal diagnosis.

Diagnosis of fetal osteogenesis imperfecta by multidisciplinary assessment: a retrospective study of 10 cases.

OBJECTIVE: To describe our 2 year experience in diagnosing prenatal-onset osteogenesis imperfecta (OI) by multidisciplinary assessment. METHODS: We retrospectively analyzed 10 cases of fetal OI by using prenatal ultrasound evaluation, postnatal radiographic diagnosis, and molecular genetic testing of COL1A1/2. RESULTS: By postnatal radiographic examination, five patients were diagnosed with type II OI and five were diagnosed with type III OI. A causative variant in the COL1A1 gene was found in four cases of type II and one case of type III OI; a causative variant in the COL1A2 gene was found in two cases of type III OI. CONCLUSION: The definitive diagnosis of fetal OI should be accomplished using a multidisciplinary assessment, which is paramount for proper genetic counseling. With the discovery of COL1A1/2 gene variants as a cause of OI, sequence analysis of these genes will add to the diagnostic process.

Genomic insights into prenatal diagnosis of congenital heart defects: value of CNV-seq and WES in clinical practice.

This study aimed to assess the efficiency of CNV-seq and WES in detecting genetic cause of congenital heart disease (CHDs) in prenatal diagnoses and to compare CNV detection rate between isolated and non-isolated CHD cases. We conducted a retrospective study of 118 Chinese fetuses diagnosed with CHD by prenatal ultrasound. Participants underwent CNV-seq and, if necessary, WES to detect chromosomal and single nucleotide variations. The overall detection rate for pathogenic or likely pathogenic chromosomal abnormalities was 16.9%, including 7.6% aneuploidies and 9.3% pathogenic/likely pathogenic copy number variations (CNVs), predominantly 22q11.2 deletion syndrome (54.4%). The sensitivity and specificity of CNV-Seq for detecting P/Lp CNVs were 95% and 100%, respectively. CNV-Seq offered a 6.7% improvement in detecting chromosomal abnormalities over karyotyping. WES further identified significant single nucleotide and small indel variations contributing to CHD in genes such as TMEM67, PLD1, ANKRD11, and PNKP, enhancing diagnostic yield by 14.8% in cases negative for CNVs. Non-isolated CHD cases exhibited higher rates of detectable chromosomal abnormalities compared to isolated cases (32.4% vs. 9.9%, p = 0.005), underlining the genetic complexity of these conditions. The combined use of CNV-seq and WES provides a comprehensive approach to prenatal genetic testing for CHDs, unveiling significant genetic cause that could impact clinical management and parental decision-making. This study supports the integration of these advanced genomic technologies in routine prenatal diagnostics to increase detection diagnostic yields of causal genetic variants associated with CHDs.

Investigation of the frequencies of prenatally diagnosed fetal chromosomal abnormalities at a single institution.

The objective of this study was to investigate, retrospectively, the frequencies of fetal chromosomal abnormalities identified in 4176 prenatal cytogenetic examinations at the Xiamen Maternity and Child Health Care Hospital over the 5-year period from October 2005 to September 2010. The frequency of abnormal fetal karyotypes was 4.6%. Numerical chromosome abnormalities were identified in 150 cases. The frequency of trisomy 21 was by far the highest, followed by trisomy 18. Structural aberrations of chromosomes were identified in 43 cases, including 21 cases with balanced and 22 cases with unbalanced chromosomal aberrations. In addition, 16 cases of apparently de novo chromosomal aberrations and 27 cases of familial inheritances were observed. Increased awareness of the frequencies of fetal chromosome abnormalities is important for the improvement of prenatal care and providing the options of termination or continuation of the pregnancy. Data obtained in this study provide the basis of a database for genetic counseling.

[Genetic counseling and clinical outcome of fetus with de novo chromosomal aberrations].

OBJECTIVE: To analyze the chromosome rearrangements and clinical outcome in fetus detected at prenatal diagnosis, and provide information for genetic counseling about de novo chromosomal aberrations. METHODS: From January 2006 to December 2009, we found 12 cases of de novo chromosomal aberrations in 2 583 cases of prenatal cytogenetic analyses and reviewed the karyotypes, other experimental analyses data, fetal ultrasound findings and clinical outcomes. RESULTS: Out of the 12 de novo chromosomal aberrations, 10 had unbalanced translocations and 2 had balanced reciprocal translocations. Eight of the 10 unbalanced translocation cases were terminated therapeutically, and 2 were delivered with full term. Neonates were phenotypically normal in the 2 cases with unbalanced translocations, but 1 had language retardation when followed up. The two balanced translocation cases were delivered with full term, and the neonates were phenotypically normal and clinical examinations were normal too. CONCLUSION: Detailed cytogenetic and molecular study will be adjunctive tools for predicting the phenotype of fetus with de novo chromosomal aberrations. Fetal ultrasound examination will provide convincible demonstration to determine the outcome of pregnancy.

Performance evaluation of urban environmental governance in Anhui Province based on spatial and temporal differentiation analyses.

When the process of urbanization has brought economic benefits in the Yangtze River Delta of China, environmental pollution becomes increasingly prominent. In order to achieve integrated sustainable green development and reduce the gap in environmental governance performance between regions, this study analyzed the environmental issues of provincial cities in Anhui Province from 2013 to 2017 in the urban agglomeration of Yangtze River Delta. Governance performance is analyzed and the evaluation index system framework is determined using the "pressure-state-response" model with the panel and spatial data. Based on the global principal component analysis method and spatial autocorrelation analysis, the environmental governance performance of Anhui Province has generally increased steadily from 2013 to 2017. The situation in northern Anhui is still developing in a good state. Southern Anhui is in a trend of rising first and then stabilizing, whereas central Anhui has a downward trend after a rapid rise; in terms of the spatial pattern, the overall situation is central Anhui > northern Anhui > southern Anhui. The urban spatial distribution pattern of the region shows a positive spatial correlation. Particularly, the performance levels of Maanshan City and Huainan City have been at a poor level for a long time, whereas Hefei and Huangshan have strong comprehensive environmental governance capabilities with average efficiency values of 0.55 and 0.47, respectively. Corresponding countermeasures have been proposed to rectify polluting enterprises and optimize structure of industries, increase scientific and technological investment and infrastructure construction, strengthen the radiation driving effects, and establish a pollution monitoring system. Based on all the analyses and resulted findings, we concluded the study with corresponding policy implications/suggestions and recommended countermeasures.

Prenatal diagnosis of familial recessive PIGN mutation associated with multiple anomalies: A case report.

OBJECTIVE: We present a novel homozygous splice site mutation in the PIGN gene identified by whole exome sequencing and explored the genotype-phenotype correlation. CASE REPORT: A healthy 32-year-old woman underwent an ultrasound at 13 + 5 weeks of gestation. The ultrasound revealed multiple anomalies again including cystic hygroma, omphalocele and a ventricular septal defect. The pregnancy was subsequently terminated, and whole exome sequencing revealed a novel homozygous splice site mutation in the PIGN gene c.963 G > A (p.Gln321Gln). The same variant was also detected by pedigree-based Sanger sequencing in both parents as heterozygous, while they had normal karyotypes. CONCLUSION: Our case report enhances the phenotype-genotype correlation associated with homozygous loss of function mutations in the PIGN gene.

Assessing the corporate green technology progress and environmental governance performance based on the panel data on industrial enterprises above designated size in Anhui Province, China.

Assessing the corporate green technology progress and environmental governance performance is essential to estimate the technological levels and environment regulation capabilities of enterprises. With the official statistics of collected panel data, we estimate and evaluate the differential levels of provincial corporate green technology and environmental governance performance of industrial enterprises above designated size (IEADSs) in Anhui Province across multiple dimensions. We firstly chose each surveyed city as the decision-making unit (DMU) in data envelopment analysis (DEA). Subsequently, we estimated the green technology efficiency of IEADSs from a static perspective by using the bootstrap DEA model and an improved super-efficiency (SE) DEA model. Secondly, we used the algorithm of Malmquist productivity index to analyze the dynamic efficiency development tendency and spatiotemporal characteristics in the DMUs. From a dynamic perspective, the evolutionary divergence and convergence characteristics of provincial green technology efficiency were brought about by the estimating algorithm of Malmquist productivity index based on the different regional divisions in Anhui Province. Furthermore, in combination with Malmquist-data envelopment analyses, we also used gray correlation analysis to analyze and evaluate the influencing factors of the industrial green technology efficiencies. This study shows many interesting findings across multiple dimensions. Among the 16 DMUs, there are only eight with the regional green technology efficiencies of IEADSs greater than the expected threshold of 0.9. Nevertheless, the green technology efficiencies of provincial industrial enterprises are still far from the national optimized goals in most of the surveyed cities. The regional green technology efficiencies of IEADSs were ranked as South Anhui > North Anhui > Middle Anhui. The overall average industrial green technology efficiency is 0.8650 in Anhui Province, but the provincial differences of sub-area distribution are relatively large and heterogeneous. The average provincial industrial green technology efficiency appeared as the overall tendency to rise, fall, and then rise, although there is an average bootstrapped Malmquist productivity indices of 1.009 in Anhui Province. Among the declined provincial Malmquist productivity indices, the effch, techch, and sech indices are vital causers of the overall decline of the provincial Malmquist productivity indices. Ultimately, based on all these quantitative estimates and findings, we put forward the following concluding remarks with policy implications and corresponding strategies.

Overexpression of the PLK4 Gene as a Novel Strategy for the Treatment of Autosomal Recessive Microcephaly by Improving Centrosomal Dysfunction.

Autosomal recessive microcephaly and chorioretinopathy (MCCRP) is a neurodevelopmental disorder characterized by delayed psychomotor development, growth retardation with dwarfism, and ocular abnormalities, and its occurrence has been found to be closely related to variants of the gene encoding centrosomes. However, the association between centrosomal duplication defects and the etiology of microcephaly syndromes is poorly understood. It is well known that polo-like kinase 4 (PLK4) is a key regulator of centriole duplication, and the abnormalities of centrosomal function caused by its protein variation need to be further explored in the pathogenesis of microcephaly. In our study, we found that a patient with microcephaly and chorioretinopathy harbored compound heterozygous missense variants NM_014264.4: c.2221C > T (p.Gln741*) and NM_014264.4: c.2062 T > C (p.Tyr688His) in the PLK4 gene. Overexpression experiments of the variant PLK4 proteins then showed that the G741 variant rather than the T688H variant had lost centrosomal amplification ability, and the G741 variant but not the T688H variant induced centrosomal replication disorder, which further inhibited cell proliferation, cycle division and cytoskeleton morphology in HeLa cells. Moreover, the overexpression of the two variant proteins had inconsistent effects on the target protein PLK4 by western blot analysis, also indicating that T688H variant overexpression is not functionally equivalent to WT-PLK4 overexpression. Therefore, all data support the idea that the PLK4 mutation induces centriolar duplication disorder and reduces the efficiency of mitosis inducing cell death or cell proliferation in the etiology of microcephaly disorder.

Empirical analysis of the intelligent influence factors of social network services effectiveness in e-commerce based on human learning behaviors.

Background: It is crucial for companies to understanding users' choices and learning behaviors, and the corresponding influencing factors and cognitive patterns regarding social network services to communicate with potential customers. Methods: In this study, a casual structural model was constructed and developed to model and characterize the relationships between problems to be resolved as antecedent variables and success factors as consequent variables with the intermediary variables based on human learning behaviors, whereas the concept of social network service was introduced to summarize the current issues of social network services and empirically factors affecting effectiveness of social network services. Discussion: This study highlighted the corporate need to examine the intelligent role and learning effectiveness of social network services when studying social creativity and intelligence in a social networking environment. Firstly, the framework and hypotheses of social network services were introduced to summarize the current issues of social network services and the main influencing factors affecting the working patterns of social network services. Subsequently, the empirically established model was further tested to explore the possible meaningful relationships among those variables used. Results: The study revealed that the social network services provider and the customer should improve their social creativity and community collaboration; these could be expanded and enhanced by increasing the social intelligence to raise the social network services' effect and the customer's externalization. Furthermore, social intelligence, community collaboration, and customer externalization were factors significantly influencing customers' social creativity, while the customer externalization and community collaboration were the two important factors affecting social intelligence. Conclusion: The study implied that social network services providers should provide more and more intelligent and inspiring services for their customers.

The impact of differentiated technological innovation efficiencies of industrial enterprises on the local emissions of environmental pollutants in Anhui province, China, from 2012 to 2016.

The study was designed to evaluate the impact of differentiated technological innovation efficiencies of industrial enterprises on the local emissions of environmental pollutants in Anhui province, China, during the period of 2012-2016. The econometric models of DEA and SEM-PLS and Malmquist index are used to explore the potential impacts of differentiated technological innovation efficiencies of industrial enterprises on the local emissions of environmental pollutants in Anhui province. After an initial analysis of SEM-PLS model, the models of DEA and Malmquist index are used to evaluate the differentiated degrees and dynamic development levels of local technological innovation efficiencies of industrial enterprises in different regions of Anhui province. With these analyses, the study presents three main results as follows. There is a positive correlation between the technological innovation efficiencies of industrial enterprises and the technological performance levels of environmental disposal. Meanwhile, there is a large gap among the environmental disposing performances of industrial enterprises in different regions of Anhui province. There is also a large gap between the expected and actual technological performances of industrial enterprises' environmental disposal, according to the results of SEM-PLS analysis. Furthermore, there are several obvious characteristics of geographical distribution in the impact of differentiated technological innovation efficiencies of industrial enterprises on local environmental pollutant emissions observed from the results of the DEA and Malmquist index models. However, it is not consistent with the overall provincial development trend and regional distribution pattern of industrial economics in Anhui province over the period of 2012-2016. Under the rapid development of social economics and modern technological advance, there is a weak impact of differentiated technological innovation efficiency on the technological performance of industrial environmental disposal in different regions of Anhui province. Meanwhile, the environmental disposal capacity of enterprises' technological innovation become declining too. Finally, some countermeasures and policy suggestions are put forward based on the investigation and comprehensive analyses of the DEA and SEM-PLS and Malmquist index models.

Diagnosis of Prenatal-Onset Achondrogenesis Type II by a Multidisciplinary Assessment: A Retrospective Study of 2 Cases.

AIM: Achondrogenesis type II is a rare, lethal osteochondrodysplasia with considerable phenotypic heterogeneity. We describe our experience in diagnosing prenatal-onset achondrogenesis type II by a multidisciplinary assessment. METHODS: Two cases of fetal achondrogenesis type II were analyzed retrospectively using prenatal ultrasound evaluation, postnatal radiographic diagnosis, and molecular genetic testing of COL2A1. RESULTS: A causative mutation in the COL2A1 gene was found in both patients. Combined with postnatal radiographic examination, the final diagnosis of achondrogenesis type II was made. CONCLUSION: Our findings emphasize the importance of a multidisciplinary assessment for the definitive diagnosis of achondrogenesis type II, which is paramount for proper genetic counseling.