Objective This study aimed to assess the value of genetic testing in the prenatal congenital heart disease (CHD) diagnosis and evaluate the relationship between genetic variants and prenatal phenotypes. Methods A total of 235 fetuses with CHD were classified into three groups: A: isolated simple CHD, B: isolated complex CHD, and C: non-isolated CHD. All patients underwent karyotyping and copy number variation sequencing (CNV-seq), with whole-exome sequencing (WES) performed when indicated. Statistical analyses conducted using IBM SPSS assessed the diagnostic performance of the genetic testing and detection rates across CHD subtypes. Results Karyotyping and CNV-seq revealed that chromosomal abnormality detection, particularly numerical abnormalities, was significantly associated with extracardiac anomalies (p < 0.05). In contrast, the detection rates of pathogenic/likely pathogenic (P/LP) CNVs (CNV-seq, p = 0.384) and pathogenic gene variants (WES, p = 0.624) did not differ significantly among the three groups. The severity of intracardiac abnormalities, the presence of extracardiac anomalies, and the detection of genetic abnormalities significantly influenced parental decisions regarding pregnancy termination (p < 0.05). The combination of karyotyping and CNV-seq increased the detection rate by 5.11%. In karyotyping/CNV-seq-negative fetuses who underwent WES, WES increased the detection rate by 37.21% (16/43). Conclusion Combined genetic testing significantly improved the detection rate and the detection of chromosomal numerical abnormalities was strongly associated with the presence of extracardiac anomalies. Parental decisions regarding pregnancy continuation were significantly influenced by the severity of intracardiac abnormalities, the presence of extracardiac anomalies, and the identification of genetic abnormalities.
Background To report two cases of hemoglobin H (HbH) disease with routine genetic testing missed rare variants, where the phenotype was inconsistent with routine genetic testing results, explore their true genotypes and clinical characteristics, and evaluate the application value of single-molecule nanopore sequencing (CycloneSEQ platform) in detecting rare thalassemia variants. Methods Common thalassemia gene testing was performed on two adult male patients who presented with different complications. The results showed --(SEA)/alpha alpha, which was significantly inconsistent with their hematological parameters. Subsequently, long-read sequencing of the alpha-globin gene cluster was conducted using the CycloneSEQ platform (single-molecule nanopore sequencing technology), and specific primers were designed based on the results for PCR verification. Results The two patients were ultimately diagnosed with rare deletional HbH disease with the genotype -- SEA /-alpha 4.3 (NC_000016.10:g.176935-181274DEL). The deletion range includes the alpha 1 gene and is accompanied by an X-Y-Z segment recombination, which is reported here for the first time. Both patients exhibited varying degrees of anemia and complications, suggesting that the same genotype can manifest significant phenotypic heterogeneity. Conclusion Conventional thalassemia testing fails to identify rare deletional HbH disease, frequently causing genotype-phenotype discordance and diagnostic bias. The newly reported --(SEA)/-alpha(4.3) genotype with X-Y-Z recombination expands the HbH disease genotypic spectrum and confirms obvious phenotypic heterogeneity. CycloneSEQ nanopore sequencing effectively detects rare complex variants undetectable by routine methods, supporting precise diagnosis of atypical thalassemia with favorable clinical prospects.
Background Molecular assays are essential for the rapid detection of Mycobacterium tuberculosis complex (MTBC). However, head-to-head comparisons of widely used commercial assays remain limited. This study compared the diagnostic performance of three real-time PCR assays-AdvanSure TB/NTM, Cobas MTB, and Xpert MTB/RIF-using bronchial washing specimens.Methods We retrospectively analyzed molecular assay results from 3348 bronchial washing specimens obtained between January 2021 and May 2024. Among them, 740 specimens were included in a head-to-head comparison of the three assays. Diagnostic performance was evaluated using culture-confirmed MTBC as the reference standard.Results In the head-to-head comparison (n = 740), the overall concordance rate was 93.6%. Using culture-confirmed MTBC as the reference standard, the sensitivities of the AdvanSure, Cobas, and Xpert assays were 49.1%, 96.2%, and 90.6%, respectively. In smear-negative cases (n = 713), AdvanSure showed markedly lower sensitivity (30.8%) than the Cobas (94.9%) and Xpert (87.2%). AdvanSure showed the highest overall specificity (98.7%), followed by Cobas (96.9%) and Xpert (96.4%). The Xpert MTB/RIF assay demonstrated complete concordance with drug susceptibility testing for detecting rifampicin resistance, with a sensitivity of 100% (95% CI, 59.0%-100.0%) and a specificity of 100% (95% CI, 97.3%-100.0%).Conclusion In this real-world cohort with a high proportion of smear-negative cases, the Cobas and Xpert assays exhibited significantly higher sensitivity for MTBC detection than the AdvanSure assay. These findings highlight the importance of highly sensitive molecular assays for the early diagnosis of pulmonary tuberculosis, particularly in patients with low bacillary burden.
Background The objective of this study is to evaluate whether the rapid lateral flow immunochromatography Geenius HCV Supplemental Assay (ICH) can serve as an alternative to INNO-LIA HCV Score Confirmatory western blot (WB) assay in a population of blood donors.Methods Sera of 60 blood donors, anti-HCV antibodies repeatedly reactive after first line screening with Architect anti-HCV chemiluminescent immunoassay, (ABBOTT, Wiesbaden, Germany) (ICL) were evaluated for anti-HCV antibodies with Geenius HCV Supplemental assay (Bio-Rad. Marnes-la-Coquette-France) (ICH) and Inno-LIA HCV Score (Inogenetics NV. Gent. Belgium) (Inno-LIA WB). The level of agreement between ICH and WB results was determined by kappa statistics.Results Out of 60 samples identified as anti-HCV antibodies repeatedly reactive by ICL, ICH identified 32% samples as reactive and 2% as indeterminate. WB identified 35% samples as positive and 20% as indeterminate. Kappa analysis detected moderate agreement between ICH and WB in detecting anti-HCV antibodies (kappa = 0.60). Moderate to almost very good agreement is acknowledged between ICH and WB in reactivity with individual HCV antigens.Conclusion Given the limited number of samples analyzed in this study we can summarize that Geenius HCV Supplemental and Inno-LIA WB assays are comparable pertaining to anti-HCV positive samples, but with discrepancy in results occurring in the area of samples classified with WB assay as indeterminate. However, there is very good agreement between Inno-LIA WB and Geenius ICH positivity/reactivity with individual HCV antigens. Our findings indicate that Geenius ICH Supplemental test cannot replace anti-HCV Inno-LIA WB in confirming anti-HCV antibodies.
ABSTRACT Background Polygenic risk scores (PRS) capture cumulative germline susceptibility and have demonstrated clinical relevance in multiple complex diseases. However, data on PRS performance in mature B‐cell neoplasms remain limited, particularly in East Asian populations. Methods We analyzed 246 Korean patients with mature B‐cell neoplasms and related plasma‐cell disorders. GWAS‐derived susceptibility variants were filtered for genome‐wide significance and pruned for linkage disequilibrium using the 1000 Genomes East Asian (EAS) reference population, followed by cross‐dataset genotype harmonization. A 37‐SNP cross‐entity score was constructed together with phenotype‐matched PRS for multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and diffuse large B‐cell lymphoma (DLBCL). Results The overall 37‐SNP score was modestly but significantly higher in cases than in the 1000 Genomes EAS reference population ( p = 0.024; OR per 1‐SD, 1.19; 95% CI, 1.02–1.38). A more distinct association emerged for MM: the MM‐specific PRS was associated with higher odds of disease (OR per 1‐SD, 1.386; 95% CI, 1.149–1.672; p = 0.000642), whereas CLL and DLBCL were not significant. Although discrimination remained modest (AUC, 0.594 for MM), MM cases were enriched above the EAS 95th percentile (OR, 2.21; p = 0.026), and rs7193541 and rs6599175 remained significant after false‐discovery‐rate correction. Conclusions Ancestry‐informed PRS identified a detectable polygenic component in Korean patients with mature B‐cell malignancies and related plasma‐cell disorders, with the most consistent evidence observed for MM. These findings support further evaluation of disease‐specific, ancestry‐informed PRS approaches rather than broadly aggregated susceptibility models.
