Prenatal phenotypes and pregnancy outcomes of fetuses with 16p11.2 microdeletion/microduplication.

BACKGROUND: Chromosomal 16p11.2 deletions and duplications are genomic disorders which are characterized by neurobehavioral abnormalities, obesity, congenital abnormalities. However, the prenatal phenotypes associated with 16p11.2 copy number variations (CNVs) have not been well characterized. This study aimed to provide an elaborate summary of intrauterine phenotypic features for these genomic disorders. METHODS: Twenty prenatal amniotic fluid samples diagnosed with 16p11.2 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed in parallel. The pregnancy outcomes and health conditions of all cases after birth were followed up. Meanwhile, we made a pooled analysis of the prenatal phenotypes in the published cases carrying 16p11.2 CNVs. RESULTS: 20 fetuses (20/20,884, 0.10%) with 16p11.2 CNVs were identified: five had 16p11.2 BP2-BP3 deletions, 10 had 16p11.2 BP4-BP5 deletions and five had 16p11.2 BP4-BP5 duplications. Abnormal ultrasound findings were recorded in ten fetuses with 16p11.2 deletions, with various degrees of intrauterine phenotypic features observed. No ultrasound abnormalities were observed in any of the 16p11.2 duplications cases during the pregnancy period. Eleven cases with 16p11.2 deletions terminated their pregnancies. For 16p11.2 duplications, four cases gave birth to healthy neonates except for one case that was lost to follow-up. CONCLUSIONS: Diverse prenatal phenotypes, ranging from normal to abnormal, were observed in cases with 16p11.2 CNVs. For 16p11.2 BP4-BP5 deletions, abnormalities of the vertebral column or ribs and thickened nuchal translucency were the most common structural and non-structural abnormalities, respectively. 16p11.2 BP2-BP3 deletions might be closely associated with fetal growth restriction and single umbilical artery. No characteristic ultrasound findings for 16p11.2 duplications have been observed to date. Given the variable expressivity and incomplete penetrance of 16p11.2 CNVs, long-term follow-up after birth should be conducted for these cases.

Fall Detection System Based on Point Cloud Enhancement Model for 24 GHz FMCW Radar.

Automatic fall detection plays a significant role in monitoring the health of senior citizens. In particular, millimeter-wave radar sensors are relevant for human pose recognition in an indoor environment due to their advantages of privacy protection, low hardware cost, and wide range of working conditions. However, low-quality point clouds from 4D radar diminish the reliability of fall detection. To improve the detection accuracy, conventional methods utilize more costly hardware. In this study, we propose a model that can provide high-quality three-dimensional point cloud images of the human body at a low cost. To improve the accuracy and effectiveness of fall detection, a system that extracts distribution features through small radar antenna arrays is developed. The proposed system achieved 99.1% and 98.9% accuracy on test datasets pertaining to new subjects and new environments, respectively.

[Preimplantation genetic testing for a Chinese pedigree affected with Rett syndrome].

OBJECTIVE: To carry out preimplantation genetic testing (PGT) for a Chinese pedigree affected with Rett syndrome (RTT). METHODS: A pedigree affected with RTT who had presented at the First Hospital of Jilin University on June 4, 2021 was selected as the study subject. Variant of the MECP2 gene was analyzed by next generation sequencing (NGS) and Sanger sequencing. Direct sequencing was also used to determine the carrier status for the c.925C>T variant of the MECP2 gene in the blastocysts, and Sanger sequencing was used to validate the results. The MECP2 gene and 168 effective single nucleotide polymorphism (SNP) loci within 2 Mb ranges up- and downstream of the gene were used to construct a haplotype for analyzing the variant site in the embryos, and embryos without the variant were subjected to the analysis for chromosomal aneuploidies. RESULTS: PGT analysis revealed that five out of seven blastocysts did not harbor the pathogenic variant. The results of aneuploidy analysis indicated that two out of five blastocysts without the variant were euploid. Following genetic counselling, the couple had opted to transplant the optimal blastocyst. Following clinical pregnancy, prenatal diagnosis showed that the fetus has a normal chromosomal karyotype, and the c.925C>T variant was not detected in the amniotic fluid sample. A healthy girl was born by Cesarean section at full term. CONCLUSION: NGS can attain efficient PGT detection and reduce the risk of disease recurrence in families affected with RTT.

Revealing the CO2 Conversion at Electrode/Electrolyte Interfaces in Li-CO2 Batteries via Nanoscale Visualization Methods.

Lithium-carbon dioxide (Li-CO2 ) battery technology presents a promising opportunity for carbon capture and energy storage. Despite tremendous efforts in Li-CO2 batteries, the complex electrode/electrolyte/CO2 triple-phase interfacial processes remain poorly understood, in particular at the nanoscale. Here, using in situ atomic force microscopy and laser confocal microscopy-differential interference contrast microscopy, we directly observed the CO2 conversion processes in Li-CO2 batteries at the nanoscale, and further revealed a laser-tuned reaction pathway based on the real-time observations. During discharge, a bi-component composite, Li2 CO3 /C, deposits as micron-sized clusters through a 3D progressive growth model, followed by a 3D decomposition pathway during the subsequent recharge. When the cell operates under laser (λ=405 nm) irradiation, densely packed Li2 CO3 /C flakes deposit rapidly during discharge. Upon the recharge, they predominantly decompose at the interfaces of the flake and electrode, detaching themselves from the electrode and causing irreversible capacity degradation. In situ Raman shows that the laser promotes the formation of poorly soluble intermediates, Li2 C2 O4 , which in turn affects growth/decomposition pathways of Li2 CO3 /C and the cell performance. Our findings provide mechanistic insights into interfacial evolution in Li-CO2 batteries and the laser-tuned CO2 conversion reactions, which can inspire strategies of monitoring and controlling the multistep and multiphase interfacial reactions in advanced electrochemical devices.

Ultrasensitive electrochemical detection and inhibition evaluation of DNA methyltransferase based on cascade strand displacement amplification.

An electrochemical sensing approach for ultrasensitive DNA methyltransferase (MTase) activity assay is proposed. After specific cleavage reaction in the presence of a methylated state, strand displacement polymerization (SDP) is initiated in the solution. The product of upstream SDP further triggers downstream SDP, which enriches abundant electrochemical species at the electrode. The whole process is quite convenient with shared enzymes. Due to the cascade signal amplification, ultrahigh sensitivity is promised. Inhibitor screening results are also demonstrated to be good. Besides, target MTase can be accurately determined in human serum samples, confirming excellent practical utility. This work provides a reliable approach for the analysis of MTase activity, which is of vital importance for related biological studies and clinical applications.

Nomogram for predicting the risk of preterm birth in women undergoing in vitro fertilization cycles.

BACKGROUND: The aim of this study was to develop a nomogram for predicting the risk of preterm birth in women undergoing in vitro fertilization (IVF) cycles. METHODS: A retrospective study of 4266 live birth cycles collected from January 2016 to October 2021 at the Center for Reproductive Medicine, First Hospital of Jilin University was performed. The sample size was sufficient based on the minimal ten events per variable (EPV) rule. The primary outcome of this study was preterm birth. The cycles were divided into the preterm birth group (n = 827) and the full-term delivery group (n = 3439). A nomogram was established based on the multivariate logistic regression analysis results. The area under the curve (AUC) was calculated to assess the prediction accuracy of the nomogram model. The calibration curve was used to measure the calibration of the nomogram. RESULTS: Multivariate logistic regression analyses showed that female obesity or overweight (OR = 1.366, 95% CI: 1.111-1.679; OR = 1.537, 95% CI: 1.030-2.292), antral follicle count (AFC) of more than 24 (OR = 1.378, 95% CI: 1.035-1.836), multiple pregnancies (OR = 6.748, 95% CI: 5.559-8.190), gestational hypertension (OR = 9.662, 95% CI: 6.632-14.078) and gestational diabetes (OR = 4.650, 95% CI: 2.289-9.445) were the independent risk factors for preterm birth in IVF patients. The area under curve (AUC) under the receiver operating characteristic (ROC) curve in the prediction model was 0.781(95%CI: 0.763-0.799). The calibration curve of the nomogram showed that the prediction model had a good calibration. CONCLUSIONS: We used five risk factors to conduct a nomogram to predict preterm birth rates for patients undergoing IVF cycles. This nomogram can provide a visual assessment of the risk of preterm birth for clinical consultation.

Fate of antibiotic resistance genes and bacteria in a coupled water-processing system with wastewater treatment plants and constructed wetlands in coastal eco-industrial parks.

In coastal eco-industrial zones, wastewater treatment plants (WWTPs) and constructed wetlands (CWs) can alleviate the challenge of water shortage and the negative effect of sewage discharge, while the problems of antibiotic resistance genes (ARGs) have not attracted enough attention. In this research, the Wafergen SmartChip system was adopted to investigate the ARG profiles in a coupled system combined WWTPs and CWs in a coastal industrial park. Potential risks of antibiotic resistance in chemical industrial wastewater were confirmed due to the higher abundance of target ARGs (> 107 copies/mL). General decline with partial enrichment in absolute and relative abundance of ARGs from the WWTPs to CWs revealed the effective removal of ARGs in the coupled system, while the fate of different ARG types varied greatly. Aminoglycoside and sulfonamide ARGs were detected with higher abundance (up to 5.34 ×107 and 3.61 ×107 copies/mL), especially aac(6')-Ib and sul1. Denitrification, secondary sedimentation, and acid hydrolysis contributed to the removal of aminoglycoside, sulfonamide, ß-lactamase, chloramphenicol, and multidrug ARGs. Catalytic ozonation contributed to the removal of tetracycline and MLSB ARGs. Subsurface CWs worked effectively for the removal of sulfonamide, tetracycline, and multidrug ARGs, especially tetX, cphA, tetG, and strB. Close correlations between ARGs and MGEs emphasized the vital roles of anthropogenic pollutants and horizontal gene transfer on the diffusion of ARGs. Actinobacteria, Bacteroidota, and Cyanobacteria were dominant in the CWs, while Proteobacteria, Firmicutes, and Planctomycetota were prevalent in the WWTPs. Redundancy analysis and variance partitioning analysis indicated that transposase and water quality posed greater influences on the distribution of ARGs. Co-occurrence network revealed that potential multiple antibiotic resistant pathogenic bacteria decreased in the CWs. The coupled system has a limited effect on the reduction of ARGs and potential ARG hosts, providing a comprehensive insight into the fate of ARGs in conventional water-processing systems.

Comparison of embryo implantation potential between time-lapse incubators and standard incubators: a randomized controlled study.

RESEARCH QUESTION: What are the potential clinical benefits of embryo culture and assessment in a time-lapse incubator compared with a standard incubator using static assessment? DESIGN: This large multicentre, single-blinded, randomized controlled study included 1224 participants randomly assigned (1:1) to the time-lapse or standard incubator group. In all patients one or two embryos were transferred on day 3. The primary outcome was the implantation rate in the first embryo transfer cycle. Secondary outcomes included the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate. RESULTS: Among 1224 participants recruited, 1182 underwent embryo transfer. The number of successfully implanted embryos in the first transfer cycle was significantly higher in the time-lapse incubator group (time-lapse group: 52.35%, standard incubator group: 47.11%, P = 0.014). The implantation rate in the first embryo transfer cycle was still significantly higher in the time-lapse group than the standard incubator group after adjusting for age, body mass index, medical centre and embryo status (relative risk 1.11, 95% confidence interval 1.02-1.20, P = 0.020). However, the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate were not statistically different between the groups. CONCLUSIONS: The implantation rate in the first embryo transfer cycle was significantly improved in the time-lapse group, but the effect of the time-lapse system on the cumulative implantation rate or cumulative live birth rate was not significant. The embryo assessment method offered by time-lapse systems rather than an undisturbed environment may play an important role in improving the implantation rate in the first embryo transfer cycle. These results are only applicable to young patients.

Incidence and risk factors for early pregnancy loss in women with first pregnancy undergoing in vitro fertilization-embryo transfer.

BACKGROUND: This study aimed to explore the incidence and influencing factors for early pregnancy loss (EPL) in infertility patients with first pregnancy undergoing in vitro fertilization (IVF) embryo transfer cycles in Jilin province, China. METHODS: A retrospective study of 2709 first pregnancy embryo transfer cycles collected from January 2016 to January 2021 was performed. The cycles were divided into the EPL group (n = 411) and the live birth group (n = 2298) according to the cycle outcomes. RESULTS: The EPL rate of the first-time pregnancies for infertility patients undergoing fresh/frozen-thaw embryo transfer cycle was 14.1%. Female patients aged 40 and older had increased odds of EPL compared to those under 35 (OR = 3.97, 95%CI: 2.80-7.55). Female patients with a body mass index (BMI) of 25 or greater were more likely to have EPLs than those in the normal BMI range (OR = 1.32, 95%CI: 1.03-1.70). The odds of EPL after frozen-thaw embryo transfer were higher than those after fresh embryo transfer (OR = 1.59, 95%CI: 1.11-2.27). A thin endometrium on the day of embryo transfer increased the odds of EPL (OR = 1.84, 95%CI: 1.01-3.33). Transferring more than two embryos had lower odds of EPL than single-embryo transfer (OR = 0.67, 95%CI: 0.50-0.90). Compared with other infertility diagnoses, tubal factor alone was associated with lower odds of EPL (OR = 0.72, 95%CI: 0.53-0.98). CONCLUSIONS: The risk factors for EPL were age 40 and older, obesity, frozen-thaw cycle, thin endometrium, and non-isolated tubal factor.

Derivation of predicted no effect concentration and ecological risk assessment of polycyclic musks tonalide and galaxolide in sediment.

Polycyclic musks (PMs) have drawn increased attention in recent years because of their persistence, bioaccumulation and toxicity. As two typical PMs contaminants, tonalide (AHTN) and galaxolide (HHCB) are widely detected in sediment worldwide. Acute and chronic toxicity data of AHTN and HHCB to freshwater and seawater organisms in water and sediments are collected and screened. The predicted no effect concentrations (PNECsediment) for AHTN and HHCB is derived according to the equilibrium partitioning method recommended by the EU technical guidance document (TGD) and the species sensitivity distribution (SSD) method based on the measured sediment toxicity data. The concentration levels of AHTN and HHCB are investigated and evaluated in freshwater and seawater sediments. Results show the difference between native and non-native freshwater species is not statistically significant. AHTN is more toxic to freshwater and seawater organisms than HHCB, and seawater organisms are more sensitive to 2 musks than freshwater organisms. The chronic PNECsediment values of AHTN and HHCB are 194.48 and 416.47 ng/g in freshwater sediment, 88.93 and 128.34 ng/g in seawater sediment respectively. The AHTN and HHCB linear correlation analysis exhibited a strong positive linear correlation in both domestic (R2=0.9054) and foreign (R2 = 0.9645) sediment. Preliminary risk assessment shows that the risks posed by AHTN and HHCB in sediment based on individual or combined concentrations of two musks are at medium to high levels in some regions. Further risk assessment results indicate that, for HHCB, 1.72% of foreign freshwater sediment may pose an ecological risk to 5% species; for AHTN, 8.06% of foreign freshwater sediment and 1.02% of domestic freshwater sediment may pose an ecological risk to 5% species, and 5.86% of seawater sediment may pose an ecological risk to 5% species. The above results indicate that there are some negligible risks in domestic and foreign sediments posed by these two musks, we should continue to pay attention to the toxic effects and pollution level of both musks in environment.

Real-Time Non-Contact Millimeter Wave Radar-Based Vital Sign Detection.

In this paper, the extraction of the life activity spectrum based on the millimeter (mm) wave radar is designed to realize the detection of target objects and the threshold trigger module. The maximum likelihood estimation method is selected to complete the design of the average early warning probability trigger function. The threshold trigger module is designed for the echo signal of static objects in the echo signal. It will interfere with the extraction of Doppler frequency shift results. The moving target detection method is selected, and the filter is designed. The static clutter interference is filtered without affecting the phase difference between the detection sequences, and the highlight target signal is improved. The frequency and displacement of thoracic movement are used as the detection data. Through the Fourier transform calculation of the sequence, the spectrum value is extracted within the estimated range of the heartbeat and respiration spectrum, and the heartbeat and respiration signals are picked up. The proposed design uses Modelsim and Quartus for CO-simulation to complete the simulation verification of the function, extract the number of logical units occupied by computing resources, and verify the algorithm with the vital signs experiment. The heartbeat and respiration were detected using the sports bracelet; the relative errors of heartbeat detection were 0-6.3%, the respiration detection was 0-9.5%, and the relative errors of heartbeat detection were overwhelmingly less than 5%.

[Family analysis of a child with Short-rib polydactyly syndrome type III due to variant of DYNC2H1 gene].

OBJECTIVE: To report on the clinical characteristics of a family of short-rib polydactyly syndrome type III and its pathogenic variants. METHODS: Muscle samples from the the third fetus was collected after the induction of labor, and peripheral blood samples of its parents and grandparents were also collected. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variants were verified by Sanger sequencing of the family. RESULTS: The proband was found to harbor a c.9819+1G>A variant and a c.4625C>A variant of the DYNC2H1 gene, which were respectively inherited from its mother and father. Sanger sequencing verified that the family has fit the autosomal recessive inheritance. CONCLUSION: The c.9819+1G>A and c.4625C>A variants of the DYNC2H1 gene probably underlay the short-rib polydactyly syndrome type 3 in the proband.

Clinical Application of Chromosomal Microarray Analysis in Pregnant Women with Advanced Maternal Age and Fetuses with Ultrasonographic Soft Markers.

BACKGROUND In pregnant women with advanced maternal age (AMA) and fetuses with ultrasonographic (USG) soft markers it is always challenging to decide whether to implement chromosomal microarray analysis (CMA) or not. It is unclear whether CMA should be used in the fetuses with isolated USG soft markers, and there is still a lack of extensive sample research. MATERIAL AND METHODS We enrolled 1521 cases in our research and divided them into 3 groups as follows: pregnant women with isolated AMA (group 1, n=633), pregnant women whose fetuses had isolated USG soft markers (group 2, n=750), and pregnant women with AMA whose fetuses had isolated USG soft markers (group 3, n=138). All pregnant women underwent prenatal ultrasound and amniocentesis, and fetal cells in the amniotic fluid were used for genetic analysis of CMA. All participants signed a written informed consent prior to CMA. RESULTS Abnormal findings were detected by CMA in 330 (21.70%) fetuses, including 37 (2.43%) clinically significant copy number variations (CNVs), 52 (3.42%) benign or likely benign CNVs, and 240 (15.78%) variants of unknown significance. The frequency of clinically significant CNVs in group 1 and group 2 were significantly lower than that in group 3 (2.37% and 2.0% vs 5.07%, P<0.01). More than a half (59.46%, 22/37) of the pregnant women decided to continue their pregnancy despite having a fetus diagnosed with clinically significant CNV. CONCLUSIONS CMA can increase the diagnostic yield of fetal chromosomal abnormality for pregnant women with isolated AMA or/and their fetuses had isolated USG soft markers.

Ultrasonographic findings and prenatal diagnosis of complete trisomy 17p syndrome: A case report and review of the literature.

BACKGROUND: Trisomy of the short arm of chromosome 17 is a rare genomic disorder. The clinical features of complete trisomy 17p syndrome have been described. Most cases of this syndrome have been found in infants and children, but only a few cases were found by ultrasound in the prenatal period. METHODS: We report a case of complete trisomy 17p syndrome, which was inherited from paternal balanced translocation t(15;17)(q11.2;q11.2). A pregnant woman underwent an ultrasound examination at 24 weeks of gestation. Amniotic fluid was collected by amniocentesis. Cytogenetic and single nucleotide polymorphism array analyses were performed. We further reviewed the relationship between duplication regions and the clinical phenotype. RESULTS: Ultrasonographic evaluation showed intrauterine growth retardation and a right choroid plexus cyst, but the gallbladder was not observed. The fetal karyotype was 46,XX,der(17)t(15;17)(q11.2;q11.2)pat. The father's karyotype was 46,XY,t(15;17)(q11.2;q11.2). The single nucleotide polymorphism array results showed arr[GRCh37] 17p13.3q11.1(525-25309337)×3, which indicated a 25.309-Mb duplication. CONCLUSION: Complete trisomy 17p syndrome shows severe malformations. Intrauterine growth retardation is the most typical manifestation of this syndrome as shown by ultrasonography in the second trimester of pregnancy. The genotype-phenotype relationships of complete trisomy 17p syndrome are not completely consistent. To further determine these relationships, additional cases are necessary to provide more information from ultrasonographic findings during pregnancy.

Molecular cytogenetic studies of a male carrier with a unique (Y;14) translocation: Case report.

BACKGROUND: Chromosome translocation is a genetic factor associated with male infertility. However, cases of Y chromosome/autosome translocation are rare. Individuals with translocation between the Y chromosome and an autosome have a variety of different clinical phenotypes. There is a need for further study of molecular cytogenetic feature of those with Y chromosome translocation. METHODS: We reported that an apparently healthy 31-year-old man, 168 cm tall and weighing 65 kg, had a 2-year history of primary infertility after marriage. Clinical diagnostic techniques included semen analysis, hormone measurements, cytogenetic analysis, fluorescence in situ hybridization (FISH), and high-throughput multiplex ligation-dependent probe amplification semiconductor sequencing. Detailed genetic counseling was provided to the patient. Intracytoplasmic sperm injection treatment combined with preimplantation genetic diagnosis was chosen with the aim of achieving a successful pregnancy. RESULTS: Semen analysis revealed cryptozoospermia. Hormone levels were within the normal limits. Sequencing results indicated the presence of the sex-determining region on Yp, and AZFa, AZFb, and AZFc regions on Yq. The patient's karyotype was 45,X,psu,dic(Y;14)(p11.3;q11.2), which was confirmed by cytogenetic analysis and FISH. CONCLUSION: This study reports a case of cryptozoospermia in a male patient with a Y;14 chromosomal translocation. When clinical karyotyping has revealed potential Y chromosome abnormality, FISH or molecular detection should be further performed to facilitate identification of the chromosomal breakpoint.

Y chromosome structural variation in infertile men detected by targeted next-generation sequencing.

PURPOSE: To provide a validated method to identify copy number variation (CNV) in regions of the Y chromosome of infertile men by next-generation sequencing (NGS). METHODS: Semen analysis was used to determine the quality of semen and diagnose infertility. Deletion of the azoospermia factor (AZF) region in the Y chromosome was detected by a routine sequence-tagged-site PCR (STS-PCR) method. We then used the NGS method to detect CNV in the AZF region, including deletions and duplications. RESULTS: A total of 326 samples from male infertility patients, family members, and sperm donors were studied between January 2011 and May 2017. AZF microdeletions were detected in 120 patients by STS-PCR, and these results were consistent with the results from NGS. In addition, of the 160 patients and male family members who had no microdeletions detected by STS-PCR, 51 cases were found to exhibit Y chromosome structural variations by the NGS method (31.88%, 51/160). No microdeletions were found in 46 donors by STS-PCR, but the NGS method revealed 11 of these donors (23.91%, 11/46) carried structural variations, which were mainly in the AZFc region, including partial deletions and duplications. CONCLUSION: The established NGS method can replace the conventional STS-PCR method to detect Y chromosome microdeletions. The NGS method can detect CNV, such as partial deletion or duplication, and provide details of the abnormal range and size of variations.

Associated factors of secondary sex ratio of offspring in assisted reproductive technology: a cross-sectional study in Jilin Province, China.

BACKGROUND: The aim of this study was to determine the secondary sex ratio (SSR) of offspring in assisted reproduction technology (ART) in Jilin Province, China, and to analyse the influencing factors associated with SSR. METHODS: A cross-sectional study of 3833 babies including singletons and twins born to 2990 couples treated by ART between May 2011 and December 2018 was performed. RESULTS: The main outcomes of this study were that the SSR of ART babies in Jilin Province was 50.64% and the SSR was associated with fertilization methods (p < 0.05). Comparing to in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) (OR = 0.808, 95%CI: 0.681-0.958) decreased the percentage of male babies. CONCLUSIONS: This study suggests that the SSR of ART births in Jilin Province was lower than the normal level and ICSI had a significant effect on SSR. Though we need more samples to study in the future, we still need to think about the impact of ICSI on SSR in ART.

The difference between karyotype analysis and chromosome microarray for mosaicism of aneuploid chromosomes in prenatal diagnosis.

OBJECTIVE: To compare karyotype and chromosomal microarray (CMA) analysis of aneuploid chromosome mosaicism in amniocentesis samples. MATERIALS AND METHODS: A total of 2091 amniocentesis samples from pregnant women were collected from March 1, 2019, to January 31, 2020. Karyotype analysis was performed using G-banding and CMA analysis used the Affymetrix CytoScan 750K SNP microarray. RESULT: Thirteen cases with aneuploid chromosome mosaicism were detected and compared between the karyotype and CMA methods. Seven of these cases were trisomic mosaicism, and the levels of mosaicism calculated from CMA were higher than those detected from karyotype analysis; noting three cases of trisomy mosaicism were not detected by karyotype analysis. Four cases exhibited monomeric mosaicism, and the levels of mosaicism detected in three of these cases were higher in karyotype compared with CMA analysis; one case had equivalent levels of monomeric mosaicism from both karyotype and CMA analysis. Two other cases from karyotype analysis were a mix of monosomic and trisomic mosaicism, whereas the CMA result was restricted to monosomic mosaicism for these cases. CONCLUSION: Both karyotype and CMA analysis can be used to detect aneuploid chromosome mosaicism. However, the two methods produced different results. CMA and karyotype analysis have their own advantages in detecting aneuploid mosaicism, and the combination of these methods provides a more rigorous diagnosis.

Identification of KISS1R gene mutations in disorders of non-obstructive azoospermia in the northeast population of China.

BACKGROUND: Non-obstructive azoospermia (NOA), a serious phenotype of male spermatogenesis failure, is a multifactorial disease which is regulated by genetic, epigenetic, and environmental factors. Some gene structural variants have been demonstrated to be related to NOA. Loss-of-function mutations of KISS1R cause normosmic idiopathic hypogonadotropic hypogonadism (IHH) which result in azoospermia at the pre-testicular level. The objective of this research was to investigate genetic variants of KISS1R in NOA patients. METHODS: The entire coding region of 52 spermatogenesis-associated genes (KISS1R included) was sequenced from 200 NOA patients. Mutation screening was performed to identify genetic variations of these genes by targeted exome sequencing. Sequencing data analysis was carried out by a series of bioinformatics tools. Candidate variants confirmation was performed by Sanger sequencing. Functional analysis of candidate variants was evaluated using SIFT and PolyPhen-2. RESULTS: Three heterozygous missense variants in KISS1R were identified in three patients, respectively. No deleterious variations in other candidate genes were found in the three patients. Two of these three variants, p.A211T and p.G186E, had been reported in the ExAC and dbSNP database, respectively, while the other variant p.A301D was novel. These variants were all predicted to be likely pathogenic by in silico analysis. CONCLUSION: Our study revealed three heterozygous missense variants in KISS1R which expanded the mutation spectrum of KISS1R in infertile men with NOA in the northeast of China.

Prenatal diagnosis of a de novo tetrasomy 15q24.3-25.3: Case report and literature review.

BACKGROUND: Terminal duplication on chromosome 15q is a rare chromosomal variation. Affected individuals show similar features such as growth dysplasia or the development of frontal bossing, body deformities, facial abnormalities, and genitourinary or cardiovascular disorders. However, it is not yet clear whether such 15q repeats lead to identifiable patterns of clinical abnormalities. Therefore, the purpose of this study was to analyze the prenatal diagnostic results and clinical manifestations of a fetus with 15q duplication and to summarize the literature. METHODS: The case was a fetus at 28 weeks of gestation. The risk of Down syndrome from second-trimester screening was 1/140. Prenatal ultrasound and amniocentesis were performed, and chromosomal microarray analysis (CMA) was used for genetic analysis. RESULTS: The fetus had abnormal clinical features, including intracardiac echogenic focus in the left ventricle, an aberrant right subclavian artery, and growth delay. The fetal chromosomal karyotype was 46,XX,15q?,12q?,21pstk+, and CMA revealed a 10.163 Mb duplication at 15q24.3-q25.3. The couple chose to terminate the pregnancy after careful consideration. CONCLUSIONS: The combination and rational application of cytogenetics technology and molecular genetics technology such as CMA will open up the field of clinical application and provide useful genetic counseling for parents of fetuses carrying such chromosomal duplications.