Curcumol: a review of its pharmacology, pharmacokinetics, drug delivery systems, structure-activity relationships, and potential applications.

Curcumol (Cur), a guaiane-type sesquiterpenoid hemiketal, is an important and representative bioactive component extracted from the essential oil of the rhizomes of Curcumae rhizoma which is also known as "Ezhu" in traditional Chinese medicine. Recently, Cur has received considerable attention from the research community due to its favorable pharmacological activities, including anti-cancer, hepatoprotective, anti-inflammatory, anti-viral, anti-convulsant, and other activities, and has also exerted therapeutic effect on various cancers, liver diseases, inflammatory diseases, and infectious diseases. Pharmacokinetic studies have shown that Cur is rapidly distributed in almost all organs of rats after intragastric administration with high concentrations in the small intestine and colon. Several studies focusing on structure-activity relationship (SAR) of Cur have shown that some Cur derivatives, chemically modified at C-8 or C-14, exhibited more potent anti-cancer activity and lower toxicity than Cur itself. This review aims to comprehensively summarize the latest advances in the pharmacological and pharmacokinetic properties of Cur in the last decade with a focus on its anti-cancer and hepatoprotective potentials, as well as the research progress in drug delivery system and potential applications of Cur to date, to provide researchers with the latest information, to highlighted the limitations of relevant research at the current stage and the aspects that should be addressed in future research. Our results indicate that Cur and its derivatives could serve as potential novel agents for the treatment of a variety of diseases, particularly cancer and liver diseases.

Social vulnerability assessment under different extreme precipitation scenarios: A case study in Henan Province, China.

Extreme precipitation usually cause grievous losses&casualties, which varies greatly under different scenarios. This paper took Henan province as an example, it innovatively constructed three different extreme precipitation scenarios and built indicators system of social vulnerability from exposure, sensitivity and resilience based on MOVE framework. Social Vulnerability Indexs(SoVI) were then calculated by mathematical models under three different reoccurrence intervals. The results show that SoVI was low in the west and high in the north. High SoVI areas expanded to the middle and south as recurrence intervals increased. SoVI in each area of Henan province increased along with the recurrence intervals at different growth rates. The larger the recurrence interval was, the faster the SoVI increased. The results indicate SoVI is greatly affected by disaster levels, which need to be incorporated into social vulnerability. This study provides not only a new thought for social vulnerability assessment, but also a reference for the policymakers to formulate related risk management policies.

Prenatal diagnosis of polycystic renal diseases: diagnostic yield, novel disease-causing variants, and genotype-phenotype correlations.

BACKGROUND: Polycystic renal disease is a frequent congenital anomaly of the kidneys, but research using chromosomal microarray analysis and exome sequencing in fetuses with polycystic renal disease remains sparse, with most studies focusing on the multisystem or genitourinary system. OBJECTIVE: This study aimed to assess the detection rate of detectable genetic causes of fetal polycystic renal disease at different levels, novel disease-causing variants, and genotype-phenotype correlations. STUDY DESIGN: This study included 220 fetal polycystic renal disease cases from January 2014 to June 2022. Cases were divided into the following 3 groups: isolated multicystic dysplastic kidneys, nonisolated multicystic dysplastic kidneys, and suspected polycystic kidney disease group. We reviewed data on maternal demographics, ultrasonographic results, chromosomal microarray analysis/exome sequencing results, and pregnancy outcomes. RESULTS: In our cohort, chromosomal microarray analysis identified 19 (8.6%) fetuses carrying chromosomal abnormalities, and the most common copy number variation was 17q12 microdeletion (7/220; 3.2%). Furthermore, 94 families chose to perform trio-exome sequencing testing, and 21 fetuses (22.3%) were found to harbor pathogenic/likely pathogenic variants. There was a significant difference in the live birth rate among the 3 groups (91/130 vs 46/80 vs 1/10; P<.001). Among 138 live birth cases, 106 (78.5%) underwent postnatal ultrasound review, of which 95 (89.6%) had a consistent prenatal-postnatal ultrasound diagnosis. CONCLUSION: For both isolated and nonisolated polycystic renal disease, our data showed high detection efficiency with both testing tools. The detection of novel pathogenic variants expands the known disease spectrum of polycystic renal disease-associated genes while enriching our understanding of the genotype-phenotype correlation. Therefore, we consider it feasible to perform chromosomal microarray analysis+exome sequencing testing in fetal polycystic renal disease. Moreover, prenatal-postnatal ultrasound concordance was greater, the live birth rate was higher, and prognosis was better when known genetic disorders were excluded, indicating that genetic testing results significantly influenced pregnancy decisions.

Association of prenatal thoracic ultrasound abnormalities with copy number variants at a single Chinese tertiary center.

OBJECTIVE: To systematically evaluate the association of prenatal thoracic ultrasound abnormalities with copy number variants (CNVs). METHODS: Chromosomal microarray (CMA) data and clinical characteristics from fetuses with thoracic ultrasound abnormalities were retrieved and analyzed. RESULTS: Thoracic ultrasound findings were mainly isolated except for fetal pleural effusion (FPE) and pulmonary hypoplasia. The diagnostic yield of CMA for thoracic anomaly was 9.66%, and FPE (17/68, 25%), pulmonary hypoplasia (1/8, 12.5%), and congenital diaphragmatic hernia (CDH) (6/79, 7.59%) indicated relatively high pathogenic/likely pathogenic (P/LP) CNV findings. The detection rate for P/LP CNVs was obviously increased in non-isolated thoracic anomalies (27.91% vs. 1.96%, P < 0.0001), non-isolated FPE (37.78% vs. 0%, P = 0.0007) and non-isolated congenital pulmonary airway malformation (CPAM) (27.27% vs. 0%, P < 0.0001), and significantly different among thoracic anomalies. Additionally, the rate of termination of pregnancy in cases with non-isolated thoracic anomalies (58.49% vs. 12.34%, P < 0.0001) and P/LP CNVs (85.71% vs. 24.15%, P < 0.0001) was obviously increased. CONCLUSION: The present study expanded phenotype spectrums for particular recurrent CNVs. FPE, CDH, and pulmonary hypoplasia indicated relatively high P/LP CNV findings among common thoracic ultrasound abnormalities, CPAM associated with other ultrasound abnormalities increased the incidence of diagnostic CNVs, while bronchopulmonary sequestration might not be associated with positive CNVs. The present data recommended CMA application for cases with prenatal thoracic ultrasound abnormalities, especially non-isolated FPE, non-isolated CPAM, CDH, and pulmonary hypoplasia.

PDIA2 variant associated with vitiligo.

The manuscript addresses an important topic: genetic analysis of Vitiligo. Vitiligo is a complicated condition and the genetic factors account for 80% of the risk. Linkage analysis for a four generations Chinese family identified 16p13.3p13.2 as the susceptibility locus of vitiligo, whole exome sequencing then identified PDIA2 as the new candidate gene. The association between the candidate gene and vitiligo requires further investigation.

A Deep-Learning-Based Method Can Detect Both Common and Rare Genetic Disorders in Fetal Ultrasound.

A global survey indicates that genetic syndromes affect approximately 8% of the population, but most genetic diagnoses can only be performed after babies are born. Abnormal facial characteristics have been identified in various genetic diseases; however, current facial identification technologies cannot be applied to prenatal diagnosis. We developed Pgds-ResNet, a fully automated prenatal screening algorithm based on deep neural networks, to detect high-risk fetuses affected by a variety of genetic diseases. In screening for Trisomy 21, Trisomy 18, Trisomy 13, and rare genetic diseases, Pgds-ResNet achieved sensitivities of 0.83, 0.92, 0.75, and 0.96, and specificities of 0.94, 0.93, 0.95, and 0.92, respectively. As shown in heatmaps, the abnormalities detected by Pgds-ResNet are consistent with clinical reports. In a comparative experiment, the performance of Pgds-ResNet is comparable to that of experienced sonographers. This fetal genetic screening technology offers an opportunity for early risk assessment and presents a non-invasive, affordable, and complementary method to identify high-risk fetuses affected by genetic diseases. Additionally, it has the capability to screen for certain rare genetic conditions, thereby enhancing the clinic's detection rate.

Nonmetallic SERS-based biosensor for ultrasensitive and reproducible immunoassay of ferritin mediated by magnetic molybdenum disulfide nanoflowers and black phosphorus nanosheets.

To improve the curability of cancer patients, it is essential to propose an early diagnosis technology with ultra-high sensitivity and reliable biocompatibility. Herein, a sophisticated nonmetallic SERS-based immunosensor, comprised by a MoS2 @Fe3O4 nanoflower-based immunoprobe with magnetism and a black phosphorus (BP) nanosheet-based immunosubstrate, was proposed for the specific in-situ monitoring of ferritin (FER). The sandwich immunosensor was endowed with an excellent SERS performance mainly ascribed to a synergistic chemical enhancement as well as an additional electrostatic adsorption effect, achieving a limit of detection down to 7.3 × 10-5 µg/mL. Particularly, all the Raman label, target FER, and anti-FER could be completely degraded within 70 min under visible light irradiation owing to the favorable photocatalytic activities of MoS2 and BP which could be then effectively separated and collected with the assistance of an external magnet. Such a recyclable nonmetallic immunosensor holds great potential and practicality in the clinical screening of cancer.

Diphenyl imidazole-based fluorescent chemosensor for Al3+ and its Al3+ complex toward water detection in food products.

A sophisticated fluorescent chemosensor, 2-(4-nitrophenyl)-4,5-diphenyl-1H-imidazole (NPDI), was designed and synthesized through a one-step condensation reaction. NPDI exhibited a fluorescence enhancement response toward Al3+, accompanied by significant emission color change without interference from other tested metal ions. The binding stoichiometry and mechanism was corroborated using various techniques. The limit of detection (LOD) for Al3+ could reach 7.25 × 10-8 mol/L and the binding constant was found to be 1.47 × 105 L/mol. Furthermore, the in-situ formed NPDI·Al complex functioned a secondary chemosensor for water by quenching effect. The fluorescence quenching mechanism could be attributed to hydrogen bonding interaction of nitro substituent with water. The LOD was calculated to be 0.012 %, indicating NPDI·Al heightened sensitivity to water. Additionally, NPDI·Al complex was employed for the moisture detection in the surroundings. Finally, the practical application of NPDI·Al complex had been successfully used in the determination of water content in food products.

Tuning the Red-to-Green-Upconversion Luminescence Intensity Ratio of Na3ScF6: 20% Yb3+, 2% Er3+ Particles by Changes in Size.

Na3ScF6: 20% Yb3+, 2% Er3+ samples were synthesized with different reaction times and reaction temperatures using the solvothermal method. We carried out a series of tests on Na3ScF6 crystals. The XRD patterns showed that the monoclinic phases of the Na3ScF6 samples could be synthesized under different reaction conditions, and doping with Yb3+ ions and Er3+ ions did not change the crystal structures. The SEM images showed that the sizes of the samples gradually increased with reaction time and reaction temperature. The fluorescence spectra showed that the emission peaks of the prepared samples under 980 nm near-infrared (NIR) excitation were centered at 520 nm/543 nm and 654 nm, corresponding to the 2H11/2/4S3/2→4I15/2 and 4F9/2→4I15/2 transitions, respectively. With the increasing size of the samples, the emission intensities at 654 nm increased and the luminescence colors changed from green to red; at the same time, the red-to-green luminescence intensity ratios (IR/IG ratios) increased from 0.435 to 15.106-by as much as ~34.7 times. Therefore, this paper provides a scheme for tuning the IR/IG ratios of Na3ScF6: 20% Yb3+, 2% Er3+ samples by changing their sizes, making it possible to enhance the intensity of red upconversion, which has great potential for the study of color displays and lighting.

SERS-based recyclable immunoassay mediated by 1T-2H mixed-phase magnetic molybdenum disulfide probe and 2D graphitic carbon nitride substrate.

Recently, non-metallic SERS-based immunoassay has attracted much attention due to its attractive chemical enhancement (CM), chemical stability, and biocompatibility. Herein, metallic (1T)-semiconductor (2H) mixed-phase magnetic molybdenum disulfide (MoS2) was rationally developed and combined with two-dimensional (2D) graphitic carbon nitride (g-C3N4) nanosheets to realize a SERS-based recyclable immunoassay of CA125. The Fe3O4 core promoted the reliable stacking of MoS2 nanoflakes into a flower-like shape with fully-exposed active surface. Particularly, the existence of 1T phase facilitated a noble-metal-comparable SERS activity due to the high electron density-induced charge transfer process with elevated efficiency. Moreover, a conversion from bulk to 2D nanosheet was swimmingly achieved for g-C3N4 via acid etching, whose large surface area full of active electrons and functional groups triggered an enhancement factor (EF) of 7.8 × 106. Based on a typical sandwich immunostructure, a limit of detection (LOD) as 4.96 × 10-4 IU/mL was demonstrated for CA125 in a recyclable process. Finally, such an immunosensor was employed to analyze clinical samples, indicating its prodigious potentiality in the early recognition and monitoring of cancer.

Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2.

The Dandy-Walker malformation (DWM) is characterized by neuron dysregulation in embryonic development; however, the regulatory mechanisms associated with it are unclear. This study aimed to investigate the role of NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4) in regulating downstream signaling cascades and neuronal proliferation and apoptosis. Ndufa4 overexpression promoted the proliferation of neurons and inhibited their apoptosis in vitro, which underwent reverse regulation by the Ndufa4 short hairpin RNAs. Ndufa4-knockout (KO) mice showed abnormal histological alterations in the brain tissue, in addition to impaired spatial learning capacity and exploratory activity. Ndufa4 depletion altered the microRNA expressional profiles of the cerebellum: Ndufa4 inhibited miR-145a-5p expression both in the cerebellum and neurons. miR-145a-5p inhibited the proliferation of neurons and promoted their apoptosis. Ndufa4 promoted and miR-145a-5p inhibited the expression of human homer protein homolog 1 and cyclin D2 in neurons. Thus, Ndufa4 promotes the proliferation of neurons and inhibits their apoptosis by inhibiting miR-145a-5p, which directly targets and inhibits the untranslated regions of Homer1 and Ccnd2 expression.

Prenatal diagnosis of ultrasound soft markers in a single medical center of mainland China.

BACKGROUND: There are a few studies on the chromosomal aberration of Ultrasound soft markers (USMs). The aim of this study was to determine the detection rate of clinically significant chromosomal abnormalities (CSCA) in fetuses with different USMs. METHODS: This study included fetuses with USMs who underwent invasive prenatal diagnosis for karyotype and/or chromosomal microarray (CMA) by categorizing into two groups: a single USM (SUSM) and multiple USMs (MUSMs). RESULTS: Of the 358 cases with USMs, CSCA occurred in 3.09% (8/259) and 8.08% (8/99) of the SUSM and MUSM groups, respectively (P < 0.05). Of 16 cases identified with CSCA, theoretically 68.75% (11/16) could be detected by karyotype, while 31.25% (5/16) could be recognized only by CMA. Among CSCA cases, the most frequent USM was an absent or hypoplastic nasal bone (62.5%, 10/16). In cases with negative karyotypes and/or CMA, follow-up results were available in 307 cases, including 292 term deliveries, 6 preterm deliveries, 8 terminations of pregnancy due to USMs, and 1 still birth. CONCLUSION: MUSMs increased the risk of chromosomal abnormalities. An absent or hypoplastic nasal bone was the most clinically significant marker either alone or in combination with other USMs. Most of SUSM had a good prognosis.

A simple AIE chemosensor based on diphenyl imidazole scaffold for 2,4,6-trinitrophenol detection and dye absorption.

Fluorescent material exhibiting aggregation-induced emission (AIE) has demonstrated to be a facile and effective method to detect 2,4,6-trinitrophenol (TNP) due to its excellent features. In this study, a novel diphenyl imidazole-based fluorescent material (DINP) was successfully synthesized via a facile method. Fluorescence spectra showed that DINP had a typical AIE effect in DMSO/water solution, and the fluorescence emission was effectively quenched by TNP without being affected by other explosives. The Stern-Volmer quenching constant of 2.70 × 105 M-1 and detection limit of 7.2 × 10-8 M demonstrated that the DINP aggregates could serve as potential chemosensor for TNP detection. The mechanism behind the quenching of fluorescence could be ascribed to the formation of ground state complex. In addition, fluorescent test strips and TLC plate prepared with the aggregates provided an easy and low cost method for TNP detection in the aqueous solution. Especially, DINP was applied to quantitatively detect the content of TNP in real water samples. Furthermore, the aggregates exhibited good selective adsorptive performance to rhodamine B dye in aqueous solution with high adsorption efficiency of 98 % in a few minutes.

Variant spectrum of F8 and F9 in hemophilia patients from southern China and 26 novel variants.

Hemophilia, an X-linked recessive disorder, is characterized by spontaneous or trauma-induced prolonged bleeding. It is classified as hemophilia A when caused by variants in the F8 gene, and hemophilia B when caused by F9 variants. Few studies have described hemophilia variants in the Chinese population. This study aimed to investigate the clinical and genetic profiles of 193 hemophilia patients from southern China. Utilizing Sanger sequencing, multiplex ligation-dependent probe amplification, gap detection, long-range PCR, and multiplex PCR, we identified both F8 and F9 gene variants. Pregnant women with a history of hemophilia A offspring underwent amniocentesis or villus sampling for the variant detection. Variants in F8 and F9 were pinpointed in 183 patients, with 26 being novel discoveries. Notably, genetic testing was absent in the initial evaluation of 133 out of 161 patients, leading to a protracted average definitive diagnosis timeline of 2 years. Remarkably, two hemophilia A cases with anticipated severe phenotypes due to protein-truncating variants presented with only moderate or mild clinical manifestations. Among the 40 fetuses tested, 34 were males, with 17 exhibiting hemizygous variants in the F8 gene. Our results contribute to the broader understanding of F8 and F9 variant spectrum and highlight the underuse of genetic analyses in southern China.

The Value of a Comprehensive Genomic Evaluation in Prenatal Diagnosis of Genetic Diseases: A Retrospective Study.

Currently, there are still many challenges in prenatal diagnosis, such as limited or uncertain fetal phenotyping, variant interpretation, and rapid turnaround times. The aim of this study was to illustrate the value of a comprehensive genomic evaluation in prenatal diagnosis. We retrospectively reviewed 20 fetuses with clinically significant copy number variants (CNVs) detected by chromosomal microarray analysis (CMA) and no further exome sequencing testing in our tertiary center between 2019 and 2020. The residual DNA from the prenatal cases was used for the parallel implementation of CNV sequencing (CNV-seq) and trio-based clinical exome sequencing (trio-CES). CMA revealed 26 clinically significant CNVs (18 deletions and eight duplications) in 20 fetuses, in which five fetuses had two or more CNVs. There were eight fetuses with pathogenic CNVs (e.g., del 1p36), nine fetuses with likely pathogenic CNVs (e.g., dup 22q11.21), and three fetuses with variants of unknown significance (VOUS, e.g., dup 1q21.1q21.2). Trio-CES identified four fetuses with likely pathogenic mutations (SNV/InDels). Of note, a fetus was detected with a maternally inherited hemizygous variant in the SLX4 gene due to a 16p13.3 deletion on the paternal chromosome. The sizes of CNVs detected by CNV-seq were slightly larger than that of the SNP array, and four cases with mosaic CNVs were all identified by CNV-seq. In conclusion, microdeletion/duplication syndromes and monogenic disorders may co-exist in a subject, and CNV deletion may contribute to uncovering additional recessive disease alleles. The application of a comprehensive genomic evaluation (CNVs and SNV/InDels) has great value in the prenatal diagnosis arena. CNV-seq based on NGS technology is a reliable and a cost-effective technique for identifying CNVs.

Evaluation of Emergency Response Capacity of Urban Pluvial Flooding Public Service Based on Scenario Simulation.

The evaluation of emergency response capability under different pluvial flooding scenarios is an essential approach to improve the emergency response capability of flood disasters. A new evaluation method of emergency response capacity of urban public services is proposed based on urban pluvial flooding scenario simulation. Firstly, inundation area and depth under different pluvial flooding scenarios are simulated based on the SCS-CN model. Following that, space densities of all indicators include inundation area and depth, road network and the emergency public service institutions. Then, the indicator weight is determined by the combined weighting method of entropy weight and coefficient of variation. Finally, the emergency response capacity index (of each pixel) is calculated based on the graph stacking method. Taking Erqi District, Zhengzhou City as an example, the emergency response capacity of public service under different urban flooding scenarios is evaluated. The results show that the spatial distribution difference of public service emergency response capacity in Erqi District, Zhengzhou City is obvious, and with the increase of the precipitation return period, the high value area of public service emergency response capability decreases gradually and the low value area increases gradually. This method takes into account the specific urban flooding scenario and the layout of public service institutions and road networks that have strong practicability. the results of the evaluation can provide a reference for the construction of urban flood emergency response capacity and provide support for emergency decision-making.

Prenatal isolated clubfoot increases the risk for clinically significant exome sequencing results.

OBJECTIVE: To examine the diagnostic yield of exome sequencing (ES) in singleton pregnancies with isolated fetal clubfoot. METHODS: Clinical data from singleton pregnancies with a sonographic diagnosis of isolated clubfoot and ES results between 2018 and 2021 were retrospectively obtained from a single referral medical center. The recorded data include maternal age, gestational age at sonographic diagnosis, the indication for genetic testing, ES results, and pregnancy outcomes. RESULTS: During the study period, 38 fetuses were prenatally diagnosed with isolated clubfoot by ultrasound and underwent ES after the copy number variant analysis was non-diagnostic. Through the trio-ES analysis, pathogenic or likely pathogenic variants were detected in 4 of 38 (10.5%) with the following genes: BRPF1, ANKRD17, FLNA, and KIF1A. All are de novo with three of autosomal dominant inheritance and one of X-linked recessive inheritance. CONCLUSION: Sonographic diagnosis of clubfoot, even isolated, increases the risk for monogenic syndromes. Exome sequencing should be an option for genetic investigation for such pregnancies.

Application of exome sequencing for prenatal diagnosis of fetal structural anomalies: clinical experience and lessons learned from a cohort of 1618 fetuses.

BACKGROUND: Exome sequencing (ES) is becoming more widely available in prenatal diagnosis. However, data on its clinical utility and integration into clinical management remain limited in practice. Herein, we report our experience implementing prenatal ES (pES) in a large cohort of fetuses with anomalies detected by ultrasonography using a hospital-based in-house multidisciplinary team (MDT) facilitated by a three-step genotype-driven followed by phenotype-driven analysis framework. METHODS: We performed pES in 1618 fetal cases with positive ultrasound findings but negative for karyotyping and chromosome microarray analysis between January 2014 and October 2021, including both retrospective (n=565) and prospective (n=1053) cohorts. The diagnostic efficiency and its correlation to organ systems involved, phenotypic spectrum, and the clinical impacts of pES results on pregnancy outcomes were analyzed. RESULTS: A genotype-driven followed by phenotype-driven three-step approach was carried out in all trio pES. Step 1, a genotype-driven analysis resulted in a diagnostic rate of 11.6% (187/1618). Step 2, a phenotype-driven comprehensive analysis yielded additional diagnostic findings for another 28 cases (1.7%; 28/1618). In the final step 3, data reanalyses based on new phenotypes and/or clinical requests found molecular diagnosis in 14 additional cases (0.9%; 14/1618). Altogether, 229 fetal cases (14.2%) received a molecular diagnosis, with a higher positive rate in the retrospective than the prospective cohort (17.3% vs. 12.4%, p<0.01). The diagnostic rates were highest in fetuses with skeletal anomalies (30.4%) and multiple organ involvements (25.9%), and lowest in fetuses with chest anomalies (0%). In addition, incidental and secondary findings with childhood-onset disorders were detected in 11 (0.7%) cases. Furthermore, we described the prenatal phenotypes for the first time for 27 gene-associated conditions (20.0%, 27/135) upon a systematic analysis of the diagnosed cases and expanded the phenotype spectrum for 26 (19.3%) genes where limited fetal phenotypic information was available. In the prospective cohort, the combined prenatal ultrasound and pES results had significantly impacted the clinical decisions (61.5%, 648/1053). CONCLUSIONS: The genotype-driven approach could identify about 81.7% positive cases (11.6% of the total cohort) with the initial limited fetal phenotype information considered. The following two steps of phenotype-driven analysis and data reanalyses helped us find the causative variants in an additional 2.6% of the entire cohort (18.3% of all positive findings). Our extensive phenotype analysis on a large number of molecularly confirmed prenatal cases had greatly enriched our current knowledge on fetal phenotype-genotype correlation, which may guide more focused prenatal ultrasound in the future. This is by far the largest pES cohort study that combines a robust trio sequence data analysis, systematic phenotype-genotype correlation, and well-established MDT in a single prenatal clinical setting. This work underlines the value of pES as an essential component in prenatal diagnosis in guiding medical management and parental decision making.

Prenatal diagnosis of 21 fetuses with balanced chromosomal abnormalities (BCAs) using whole-genome sequencing.

Balanced chromosomal abnormalities (BCAs) are the most common chromosomal abnormalities and the frequency of congenital abnormalities is approximately twice as high in newborns with a de novo BCA, but a prenatal diagnosis based on BCAs is subject to evaluation. To detect translocation breakpoints and conduct a prenatal diagnosis, we performed whole-genome sequencing (WGS) in 21 subjects who were found BCAs, 19 balanced chromosome translocations and two inversions, in prenatal screening. In 16 BCAs on non-N-masked regions (non-NMRs), WGS detected 13 (81.2%, 13/16) BCAs, including all the inversions. All the breakpoints of 12 (12/14) cases of sufficient DNA were confirmed by Sanger sequencing. In 13 interrupted genes, CACNA1E (in case 12) and STARD7 (in case 17) are known causative and PDCL was found in subject (case 11) with situs inversus for the first time. Case 12 with abnormal ultrasound reached a definitive genetic diagnosis of CACNA1E-disease, while STARD7 exon deletion has never been found causative in patients. WGS provides the possibility of prenatal diagnosis in fetuses with BCAs, and its clinical significance also lies in providing data for postnatal diagnosis.