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mutations are linked to postnatal epileptic encephalopathies, but prenatal features are poorly defined. We describe a novel frameshift mutations prenatal phenotype and genotype-phenotype correlations. A fetus with progressive cerebral anomalies underwent serial ultrasound, MRI, and whole-exome sequencing. Imaging showed persistent cavum septi pellucidi narrowing (0.9-2.6 mm at 21-30 weeks) and focal cortical thickening at the left temporoparietal junction. A heterozygous frameshift mutation (c.3043del, p.D1015Lfs*22) was identified, truncating Nav1.2 at residue 1015 and ablating critical functional domains. Protein modeling confirmed complete loss-of-function (LoF) due to α-subunit disruption. This is the first report of prenatal imaging phenotypes in frameshift mutations, featuring persistent CSP narrowing and progressive focal cortical thickening. Distinct from missense mutation-related ventriculomegaly, it suggests potential mutation-specific signatures. Unexplained CSP narrowing/cortical thickening warrants sodium channelopathy suspicion, with prioritized in fetal cortical malformation panels. Single-case limitations demand large-cohort validation for genotype-phenotype correlations.

Gastrointestinal defects and immunodeficiency syndrome (GIDID) is a rare and complex disorder characterized by concurrent dysfunction of the digestive and immune systems. Typically manifesting in infancy or early childhood, GIDID carries a severe prognosis with high early mortality rates. The syndrome has been specifically linked to mutations in the TTC7A gene located on chromosome 2p21. Although GIDID can present during the fetal period, reports of prenatal diagnosis remain exceptionally rare. In this study, we investigated a case involving a fetus with gastrointestinal abnormalities detected during prenatal screening, conceived by a consanguineous couple. Following termination of the pregnancy, whole-exome sequencing of the affected fetus revealed compound heterozygous variants (c.2378del and c.2357G>T) in the TTC7A gene (OMIM:609332). These findings provide critical insights for the prenatal diagnosis of GIDID and enhance fetal detection rate. Furthermore, this study expands the spectrum of known pathogenic mutations in the TTC7A gene and underscores the significant utility of fetal whole-exome sequencing for diagnosing this condition.

Background Currently, whole exome sequencing has been performed as a helpful complement in the prenatal setting in case of fetal anomalies. However, data on its clinical utility remain limited in practice. Herein, we reported our data of fetal exome sequencing in a cohort of 512 trios to evaluate its diagnostic yield. Methods In this retrospective cohort study, the couples performing prenatal exome sequencing were enrolled. Fetal phenotype was classified according to ultrasound and magnetic resonance imaging findings. Genetic variants were analyzed based on a phenotype-driven followed by genotype-driven approach in all trios. Results A total of 97 diagnostic variants in 65 genes were identified in 69 fetuses, with an average detection rate of 13.48%. Skeletal and renal system were the most frequently affected organs referred for whole exome sequencing, with the highest diagnostic rates. Among them, short femur and kidney cyst were the most common phenotype. Fetal growth restriction was the most frequently observed phenotype with a low detection rate (4.3%). Exome sequencing had limited value in isolated increased nuchal translucency and chest anomalies. Conclusions This study provides our data on the detection rate of whole exome sequencing in fetal anomalies in a large cohort. It contributes to the expanding of phenotypic and genotypic spectrum.

Recurrent pregnancy loss (RPL), especially the unexplained RPL, is associated with the disruption of maternal immune tolerance. However, little is known about the immune status at the decidua of RPL with embryonic chromosomal aberrations. Herein, mass cytometry (CyTOF) was used to interrogate the immune atlas at the decidua which was obtained from 15 RPL women—six with normal chromosome and nine with chromosomal aberrations—and five controls. The total frequency of CCR2 − CD11c high macrophages increased, while CD39 high NK cells and CCR2 − CD11c low macrophages decrease significantly in RPL when RPLs were stratified, compared with controls. Pro-inflammatory subsets of CD11c high macrophages increased, while less pro-inflammatory or suppressive subsets decreased statistically in RPL decidua whenever RPLs were stratified or not. However, CD11c high NK and CD161 high CD8 + T cells increased only in RPL with normal chromosome, while the inactivated and naive CD8 + /CD4 + T cells were enriched only in RPL with chromosomal aberrations. A pro-inflammatory signature is observed in RPL decidua; however, differences exist between RPL with and without chromosomal abnormalities.

Background Low-pass genome sequencing (LP GS) has been widely used for the detection of copy number variations (CNVs). As a key algorithmic parameter of LP GS, window selection may influence the performance of LP GS. However, limited studies have investigated this parameter for the detection of small CNVs. Methods To evaluate of the impact of sliding window on true positive rate, additional interpretation workload and resolution, 40 simulated samples with 19 pre-defined CNVs of various read amounts were simulated. Fifty-seven clinical cases with previously ascertained CMA results (27 positive cases and 30 negative cases) were used to further evaluate the influence of sliding window for detection sensitivity and specificity. Results In general, the true positive rate increased with the increase of sequencing depth for simulated samples. The algorithm by sliding a 10-Kb window in 1-Kb increments showed higher true positive rate, especially for CNVs < = 30 Kb. For deletions of 30 Kb, the algorithm by sliding a 10-Kb window in 1-Kb increments showed a true positive rate of 100% for all read amounts, while the algorithm by sliding a 50-Kb window in 5-Kb increments had a detection sensitivity of 80.0% even with 100 M read amount. The results of overlap analysis showed that the algorithm by sliding a 10-Kb window in 1-Kb increments showed less variability for both deletions and duplications (especially for CNVs < = 30 Kb), indicating higher detection resolution. Further combining the potential introduction of the additional interpretation workload by 10-Kb window in 1-Kb increments, 50 M reads is recommended for detecting most small CNVs. For the 57 clinical cases, the algorithm by sliding a 50-Kb window in 5-Kb increments and the algorithm by sliding a 10-Kb window in 1-Kb increments showed detection sensitivity of 85.19% (23/27) and 96.30% (26/27), respectively. The algorithm by sliding a 10-Kb window in 1-Kb increments detected all the CNVs missed by sliding a 50-Kb window in 5-Kb increments except for one 25.8 Kb deletion. The specificity for both algorithms was calculated as 96.67% (29/30). Conclusion Window selection, together with sequencing depth, could influence CNV detection sensitivity and resolution of LP GS for small CNVs. This study provided a set of evaluation methods and pathways based on simulated samples and clinical cases. For CNVs < = 30 kb, 10-Kb window in 1-Kb increments and >= 50 M reads were recommended for LP GS. It would be advisable for clinical labs conducting LP GS to determine the range of sensitivity and resolution for different sliding windows and sequencing depth for CNV detection.

Gestational diabetes mellitus (GDM) is an important complication of pregnancy that poses significant threats to women and their offspring. Telomere length shortens as cellular damage increases and is associated with metabolic diseases. Telomere length in fetal leucocytes was determined in 82 infants of women with GDM (N = 82) and 65 normal pregnant women (N = 65). Women with preeclampsia (N = 45) and gestational hypertension (N = 23) were also studied. In the GDM group, telomere length was significantly shorter than normal pregnancy (P = 0.028), but there were no significant differences in fetal telomere length between preeclampsia and normal pregnancy (P = 0.841) and between gestational hypertension and normal pregnancy (P = 0.561). Regression analysis revealed that fetal telomere length was significantly associated with intrauterine exposure to GDM (P = 0.027 after adjustment for maternal age, gestational age at delivery, birth weight and fetal gender). Shortened telomere length may increase the risk of metabolic diseases in adulthood of GDM offspring.

SFAS No. 115 requires firms to recognize available-for-sale (AFS) securities at fair value with accumulated unrealized gains and losses (AUGL) recorded in accumulated other comprehensive income. Firms reclassify AUGL to net income when they realize gains and losses. We refer to the amount reclassified each period by “RECLASS.” As of 1998, SFAS No. 130 requires firms to present RECLASS prominently in their financial statements. We investigate the incremental explanatory power of RECLASS for banks’ market values and market-adjusted returns. In the market value analysis, we control for AUGL, other components of book value of equity, net income before extraordinary items and RECLASS (NIBEX other ), and other components of comprehensive income. In the returns analysis, we control for ΔAUGL, ΔNIBEX other , and extraordinary items. We find high positive coefficients on RECLASS in both analyses, consistent with investors pricing RECLASS as a relatively permanent component of net income. Exploring possible explanations for these pricing implications, we find no evidence that they are attributable to RECLASS remedying unreliable fair value measurement of AUGL. We provide three distinct analyses indicating that RECLASS’s pricing implications are explained in significant part by it helping investors predict banks’ future performance. Our results illustrate that an important type of amortized cost accounting information, realized gains and losses, remains highly useful to investors despite the overall fair-value-accounting framework for AFS securities.

Background Non-invasive prenatal screening (NIPS) is widely used as the alternative choice for pregnant women at high-risk of fetal aneuploidy. However, whether NIPS has a good detective efficiency for pregnant women at advanced maternal age (AMA) has not been fully studied especially in Chinese women. Methods Twenty-nine thousand three hundred forty-three pregnant women at AMA with singleton pregnancy who received NIPS and followed-up were recruited. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), receiver operating characteristic (ROC) curves and the Youden Index for detecting fetal chromosomal aneuploidies were analyzed. The relationship between maternal age and common fetal chromosomal aneuploidy was observed. Results The sensitivity, specificity, PPV, NPV of NIPS for detecting fetal trisomy 21 were 99.11, 99.96, 90.98, and 100%, respectively. These same parameters for detecting fetal trisomy 18 were 100, 99.94, 67.92, and 100%, respectively. Finally, these parameters for detecting trisomy 13 were 100, 99.96, 27.78, and 100%, respectively. The prevalence of fetal trisomy 21 increased exponentially with maternal age. The high-risk percentage incidence rate of fetal trisomy 21 was significantly higher in the pregnant women at 37 years old or above than that in pregnant women at 35 to 37 years old. ( Youden index  = 37). Conclusion It is indicated that NIPS is an effective prenatal screening method for pregnant women at AMA.

The strong airflow beneath a rotary drone generates a wind vortex within the rice canopy; precise control of the wind vortex distance and wind vortex area can improve pesticide utilization efficiency. This paper calculates the flight parameter curve based on the wind vortex target from the wind vortex target parameter control model of the four-rotor plant protection drone, designs a flight control system using a Cube Orange flight controller and a Jetson AGX Xavier onboard computer, and implements flight parameter control using both PID control and fuzzy control algorithms. Experimental results indicate that when using PID control and fuzzy control, the average deviation values of UAV flight altitude and speed are 0.08 m, 0.08 m/s, 0.06 m, and 0.08 m/s, respectively. When using PID control, the average distance and area errors of the target downwind and upwind are 0.17 m and 0.37 m2 and 0.20 m and 0.46 m2, respectively. The corresponding values for fuzzy control are 0.12 m, 0.38 m2, 0.09 m, and 0.31 m2. In the twelve voyage experiments, the target parameter variance using fuzzy control was relatively smaller for eight voyages compared to PID control, which had a smaller variance for four voyages. On the whole, the effect of fuzzy control is superior. The wind vortex control method proposed in this paper can effectively enable precise pesticide spraying by drones. This has significant implications for reducing agricultural production costs and safeguarding the natural environment.

Background TTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset. The onset and severity of the features were considered to be correlated with the types and location of the TTN variants. Methods Whole-exome sequencing was performed on three unrelated families presenting with fetal akinesia deformation sequence (FADS), mainly characterized by reduced fetal movements and limb contractures. Sanger sequencing was performed to confirm the variants. RT-PCR analysis was performed. Results TTN c.38,876–2 A > C, a meta transcript-only variant, with a second pathogenic or likely pathogenic variant in trans , was observed in five affected fetuses from the three families. Sanger sequencing showed that all the fetal variants were inherited from the parents. RT-PCR analysis showed two kinds of abnormal splicing, including intron 199 extension and skipping of 8 bases. Conclusions Here we report on three unrelated families presenting with FADS caused by four TTN variants. In addition, our study demonstrates that pathogenic meta transcript-only TTN variant can lead to defects which is recognizable prenatally in a recessive manner.