Thalassemia and hemoglobinopathy are two common inherited disorders, which are highly prevalent in southern China. However, there is little knowledge on the genotypes of thalassemia and hemoglobinopathy in Southeastern China. In this study, we present a large-scale genetic detection and molecular characterization of thalassemia and hemoglobinopathy in Fujian province, Southeastern China. A total of 189414 subjects screened for thalassemia were recruited, and the hemoglobin components and levels were investigated. Furthermore, suspected common thalassemia was identified, and the suspected rare forms of common thalassemias and hemoglobinopathy were detected. Among the total subjects screened, the overall prevalence of thalassemia and hemoglobinopathy was 6.8% and 0.26%, and rare α-thalassemia genotypes HKαα, – THAI /αα and −α 27.6 /αα, and novel β-thalassemia gene mutations CD90(G → T) and IVS-I-110(G > A) were identified. Additionally, Hb Q-Thailand hemoglobinopathy and five other types of hemoglobinopathies (Hb New York, Hb J-Bangkok, Hb G-Taipei, Hb G-Coushatta and Hb Maputo) were found. The results of this 10-year large-scale study demonstrate high prevalence of thalassemia with complicated gene mutations in Southeastern China, which provides valuable baseline data for genetic counseling and prenatal diagnosis. In addition to detection of common thalassemia genes, detection of rare thalassemia genotypes and hemoglobinopathies is recommended.

Objective To analyze the non‐invasive prenatal testing (NIPT) for aneuploidy results of 31 515 singleton pregnancies in Fujian province, southeastern China, and assess its performance in low‐, moderate‐ and high‐risk pregnancies. Methods Women were categorized into groups according to whether their risk for fetal abnormality was low, moderate or high. Cell‐free plasma DNA extracted from peripheral blood samples was subjected to low‐coverage whole‐genome sequencing. Standard Z‐score analysis of the mapped sequencing reads was used to identify fetal aneuploidy, including the three main trisomies (T21, T18 and T13) and sex chromosome aneuploidy (SCA). NIPT‐positive results were confirmed by amniocentesis and karyotyping. The performance of NIPT for detection of T21, T18, T13 and SCA was assessed by calculating the sensitivity and specificity. Results The rate of chromosomal abnormality detected by NIPT in the study population was 1.38%. A higher rate of chromosomal abnormality was found in the high‐risk group (1.57%) compared to the moderate‐risk (1.05%) and low‐risk (1.18%) groups (P < 0.05). Sensitivity and specificity, respectively, were 98.96% (95/96) and 99.94% (31 274/31 292) for detection of T21, 100% (25/25) and 99.96% (31 352/31 363) for T18, 100% (7/7) and 99.97% (31 373/31 381) for T13 and 100% (61/61) and 99.74% (31 245/31 327) for SCA. Positive predictive values were high for T21 (84.07%) and T18 (69.44%) and moderate for T13 (46.67%) and SCA (42.66%). Conclusion Our findings support the application of NIPT for reliable and accurate testing of the general population of reproductive‐age women for clinically significant fetal aneuploidy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Recent studies have provided new insights into the diagnostic value of circulating microRNAs (miRNAs) for breast cancer (BCa). However, the inconsistent results between studies have prevented the widespread usage of miRNAs in clinics. To systematically assess the potential diagnostic value of circulating miRNAs in BCa, we performed a comprehensive meta-analysis. Eligible studies were retrieved by searching electronic databases. The quality of the studies was assessed on the basis of quality assessment for studies of diagnostic accuracy (QUADAS) criteria. The bivariate meta-analysis model was employed to summarize the diagnostic indices and plot the summary receiver operator characteristic (SROC) curve. A total of 15 studies were included in this meta-analysis, involving 1368 BCa patients and 849 healthy controls. Our bivariate random effects meta-analysis yielded an area under curve (AUC) value of 0.9217, with a sensitivity of 0.82 (95 % confidence interval (CI) 0.80-0.83) and specificity of 0.82 (95% CI 0.80-0.85) for the use of miRNAs in differentiating BCa patients from healthy controls. Notably, our subgroup analysis suggested that a combination of multiple miRNAs (AUC, sensitivity, and specificity of 0.9518, 0.87, and 0.88, respectively) seemed to harbor higher accuracy than single miRNA-based assays (AUC, sensitivity, and specificity of 0.8923, 0.79, and 0.77, respectively). Altogether, our data indicate that circulating miRNA profiling has a potential to be used as a screening test for BCa, among which, the detection of a combined multiple miRNAs may be a more comprehensive indicator than individual miRNA.

Background MicroRNAs (miRNAs) participate in the reactivation of γ‐globin expression in β‐thalassemia. However, the miRNA transcriptional profiles of pediatric β‐thalassemia remain unclear. Accordingly, in this study, we assessed miRNA expression in pediatric patients with β‐thalassemia. Methods Differentially expressed miRNAs in pediatric patients with β‐thalassemia were determined using microRNA sequencing. Results Hsa‐miR‐483‐3p, hsa‐let‐7f‐1‐3p, hsa‐let‐7a‐3p, hsa‐miR‐543, hsa‐miR‐433‐3p, hsa‐miR‐4435, hsa‐miR‐329‐3p, hsa‐miR‐92b‐5p, hsa‐miR‐6747‐3p and hsa‐miR‐495‐3p were significantly upregulated, whereas hsa‐miR‐4508, hsa‐miR‐20a‐5p, hsa‐let‐7b‐5p, hsa‐miR‐93‐5p, hsa‐let‐7i‐5p, hsa‐miR‐6501‐5p, hsa‐miR‐221‐3p, hsa‐let‐7g‐5p, hsa‐miR‐106a‐5p, and hsa‐miR‐17‐5p were significantly downregulated in pediatric patients with β‐thalassemia. After integrating our data with a previously published dataset, we found that hsa‐let‐7b‐5p and hsa‐let‐7i‐5p expression levels were also lower in adolescent or adult patients with β‐thalassemia. The predicted target genes of hsa‐let‐7b‐5p and hsa‐let‐7i‐5p were associated with the transforming growth factor β receptor, phosphatidylinositol 3‐kinase/AKT, FoxO, Hippo, and mitogen‐activated protein kinase signaling pathways. We also identified 12 target genes of hsa‐let‐7a‐3p and hsa‐let‐7f‐1‐3p and 21 target genes of hsa‐let‐7a‐3p and hsa‐let‐7f‐1‐3p, which were differentially expressed in patients with β‐thalassemia. Finally, we found that hsa‐miR‐190‐5p and hsa‐miR‐1278‐5p may regulate hemoglobin switching by modulation of the B‐cell lymphoma/leukemia 11A gene. Conclusion The results of the study show that several microRNAs are dysregulated in pediatric β‐thalassemia. Further, the results also indicate toward a critical role of let7 miRNAs in the pathogenesis of pediatric β‐thalassemia, which needs to be investigated further.

Bacterial artificial chromosomes (BACs)eon-Beads (BoBs) assay and copy number variation sequencing (CNV-seq) are two frequently used methods in today's prenatal diagnosis. Several studies were conducted to investigate the performance of each approach, but they were never compared side by side. In this article, a comprehensive comparison of BoBs and CNV-seq was conducted using 1876 amniotic fluid and umbilical cord blood samples collected from Fujian Maternity and Child Health Hospital between 2015 and 2019. Karyotyping was used as the gold standard for chromosome structure variation, and chromosomal microarray analysis was performed to validate inconsistent results. Overall, 174 cases of confirmed chromosome anomalies were detected, including 73 chromosomal aneuploidies, 10 mosaics, 30 pathogenic CNVs, and 61 other structural anomalies. BoBs and CNV-seq achieved a 100% concordance in all 55 pathogenic euchromosome aneuploidies, but CNV-seq had a higher detection rate in sex chromosome aneuploidy and mosaic identification. For CNV detection, all of the 20 pathogenic CNVs discovered by the BoBs assay also were identified by CNV-seq and 10 additional pathogenic CNVs were observed by CNV-seq. The results of this study showed that CNV-seq was a reliable and more favorable method in terms of detection rate, costs, and disease range. In combination with karyotyping, CNV-seq could improve the efficiency and accuracy of a prenatal diagnosis to alleviate maternal emotional anxiety and deduce birth defects.