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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. Synopsis: The diagnostic yield for CNVs and pregnancy outcomes varied significantly among prenatal thoracic ultrasound abnormalities, and phenotype spectrums for recurrent CNVs were expanded. [ABSTRACT FROM AUTHOR]

The genetic diagnosis of congenital heart defects (CHDs) is challenging because of genetic and phenotypic heterogeneity. The aim of our study was to evaluate the clinical value of whole exome sequencing (WES) in the prenatal diagnosis of CHDs in a large cohort. Trio‐based WES was performed in 260 fetuses with CHDs negative for karyotype and chromosome microarray analysis results. WES produced a diagnostic yield of 10% (26/260) in the entire cohort. Relative high diagnostic rate was observed in cases with cardiac rhabdomyoma (60%), complex CHDs (16.7%), septal defect (14.0%), and conotruncal defect (9.9%). There was no significant difference between the diagnostic yields in simple and complex CHDs groups (9.9% vs 16.7%), and in non‐isolated and isolated CHDs groups (15.7% vs 7.9%). The diagnostic yields in cases with CHDs with soft markers, CHDs with fetal growth restriction, and CHDs with other structural anomalies (syndromic CHDs) were 0 (0/13), 50% (1/2) and 18.2% (10/55), respectively. Variants of unknown significance were detected in 16 (6.2%) fetuses, and secondary findings in 7 (2.7%) cases. Variants in 14 candidate genes were identified. Our study demonstrates an incremental diagnostic yield by trio‐based WES in the prenatal diagnosis of CHDs after routine tests, not as high as expected. [ABSTRACT FROM AUTHOR]

Congenital chloride diarrhea (CCD) is an autosomal recessive hereditary disease manifested by persistent, watery, profuse diarrhea with high chloride concentration (>90 mmol/L). Postnatally, neonates suffer from hypochloremia, hyponatremia, hypokalemia, metabolic alkalosis, dehydration, developmental retardation, or even death. Prenatal diagnosis is of great importance for the prognosis of CCD. We report a prenatal recurrent case of CCD. Prenatal ultrasound revealed fetal diffuse intestinal dilation with the typical honeycomb sign and polyhydramnios with high amniotic fluid index. The whole exome capture and massively‐parallel DNA sequencing showed an abnormal mutation of Solute Carrier Family 26, Member 3 (SLC26A3), c.1039G>A (p.Ala347Thr), and the mutation sites were verified by sanger sequencing. When prenatal ultrasound shows polyhydramnios and diffuse intestinal dilation, CCD should be suspected. Molecular genetic testing can be helpful for the diagnosis. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study is to report the incidence and pregnancy outcome of autosomal aneuploidies other than common trisomies 21, 18, and 13 detected by noninvasive prenatal testing (NIPT) at a single center.Methods: Pregnant women undergoing NIPT from February 2015 to January 2018 in our center were offered expanded screening to include rare autosomal aneuploidies. Aneuploidies included extra copy chromosomes (most likely trisomies) and decreased copy chromosomes (most likely monosomies). The pregnancy outcomes of women consenting to the expanded NIPT screen were recorded.Results: Expanded NIPT was performed in 15 362 pregnancies. A total of 59 autosomal aneuploidies other than the 3 common trisomies were detected, with a positive screening rate of 0.38% (59/15 362). The screen positive rate was higher in women aged above 35 years than in those younger (0.44% vs 0.32%, P < .05). Of the screen positive results, 30.5% (18/59) were because of extra copies for chromosomes trisomy 7, 10.2% (6/59) for chromosome 22, and 8.5% (5/59) for chromosomes 8 and 16 respectively, while other choromosomes were less frequently involved. Decreased copy chromosomes were less common: 6.8% (4/59) for chromosomes 14 and 13. Mixed aneuploidies with increased copies for some chromosomes and decreased copies for others were also noted. Invasive prenatal diagnosis was performed in 61% (36/59) of the cases. Invasive test results and clinical follow-ups demonstrated that most (94.9%, 56/59) of the rare aneuploidies were false positives, probably resulting from confined placental mosaicism. Only 1 case (1.7%, 1/59) with NIPT report of extra copies of chromosome 7 and without ultrasound evidence of fetal abnormality was confirmed to be fetal mosaicism by microarray test. Uniparental disomy of whole chromosome 2 was identified by microarray analysis in 1 case with extra copy chromosome 2 detected by NIPT. Loss of heterozygocity of chromosome 7q11.23-q21.11 was detected in another case with extra copy chromosome 7. Fortunately, pregnancy outcomes of both cases were normal. Two fetal deaths attributed to severe fetal growth restriction were associated with extra copies of chromosome 16 at expanded NIPT.Conclusions: Autosomal aneuploidies other than trisomies 21, 18, and 13 are not uncommon in routine clinical NIPT practice. Extra copies of chromosomes in rare cases can be associated with uniparental disomy. Most rare aneuploidies at NIPT have good pregnancy outcomes. Thus, invasive testing should be used with caution for these aneuploidies in routine clinical practice. [ABSTRACT FROM AUTHOR]

Presented is the first enantioselective copper-catalyzed 1,6-conjugate addition of bis(pinacolato)diboron to para-quinone methides. The reaction proceeds with excellent yields and good to excellent enantioselectivities, and provides an attractive approach to the construction of optically active gem-diarylmehtine boronic esters. Additionally, the subsequent conversion of the derived potassium trifluoroborates into triarylmethanes with highly enantiospecificity was realized. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective This study aimed to detect genomic imbalances in fetuses with congenital heart defect (CHD) by high-resolution single-nucleotide polymorphism (SNP) array. Methods A total of 99 fetuses with CHDs with or without other ultrasound anomalies (including structural anomalies and soft markers) but normal karyotypes were investigated using Affymetrix CytoScan HD array. Results Clinical significant copy number variations (CNVs) were detected in 19 fetuses (19.2%). The proportion for variants of unknown significance was 3% after parental analysis. Five known microdeletion/microduplication syndromes were identified. The detection rate in CHD plus structural anomaly (27.8%) or soft marker (25%) group was higher than but not statistically different from isolated CHD group (15.9%). There was no significant difference between the detection rates in simple and complex CHD groups (20.7% vs. 16.7%). The detection rate in fetuses with CHD and neurologic defect was significantly higher than those with other types of structural anomaly (75% vs. 14.3%, P < 0.05). Conclusions Our results demonstrated the value of high-resolution SNP arrays in prenatal diagnosis of CHD; it should become an integral aspect in clinically molecular diagnosis and genetic counseling. The complexity of the cardiac defect was not related to the frequency of clinical significant CNV, but the presence of neurologic defect was related. © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To analyze adverse drug reactions (ADRs) associated with Shenmai injection and possible contributing factors. Methods We searched all clinical studies and ADR reports of Shenmai injection from the China National Knowledge Infrastructure (CNKI) database, the Data Bank of Chinese Scientific Journals (VIP), and Chinese Biomedical (CBM) database. We collected relevant information such as gender, age, allergic history, and diseases treated in ADR cases; types, occurrence times, and severity of ADRs; and menstruum and compatibility of Shenmai injection. Results Of the 1828 clinical studies of Shenmai injection, 146 (7.99%) mentioned 576 ADR cases; 181 ADR reports mentioned 246 ADR cases. The most commonly affected age group was 40 to 69 (57.32%). In 36 (14.63%) cases, patients were described as having an allergic history. The diseases treated in ADR cases were principally heart failure and coronary artery heart disease. Thirty-eight (15.45%) of the 246 ADR cases in ADR reports described anaphylactic shock, while the most common ADR reported in clinical studies was headache/dizziness. Of the 822 total reported ADR cases, 99 (12.04%) were class III, and 637 (77.50%) were class IV, and there were no fatalities. The menstruum of most Shenmai injections was 5% glucose. Incompatible drugs were given in 68 ADR cases. In ADR cases, the most common dosage of Shenmai injection was 40 to 60 ml; 215 (80.90%) ADR cases occurred in first time medication, mainly in the first 30 minutes after injection. Conclusions Current evidence shows that Shenmai injection had lower ADR occurrence, but some potential factors such as irrational compatibility, dosages may lead to a high risk of ADR. In future, clinicians should follow indications or functions to promote rational use of Chinese Medicine Injections . [ABSTRACT FROM AUTHOR]

The enantioselective conjugate addition of diethylzinc to enones (I) leads to ketones (III) in low to moderate yields and with good to high enantioselectivities. [ABSTRACT FROM AUTHOR]