Annals of Laboratory Medicine最新文献

{"title":"Enhancing Clinical Cardiac Care: Predicting In-Hospital Cardiac Arrest With Machine Learning.","authors":"Sollip Kim","doi":"10.3343/alm.2024.0696","DOIUrl":"10.3343/alm.2024.0696","url":null,"abstract":"","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"117-120"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance Evaluation of the LabGenius C-CT/NG-BMX Assay for <i>Chlamydia trachomatis</i> and <i>Neisseria gonorrhoeae</i> Detection.","authors":"Yong Kwan Lim, Oh Joo Kweon, Ae Ja Park, Hongkyung Kim, Sumi Yoon, Tae-Hyoung Kim, Mi-Kyung Lee","doi":"10.3343/alm.2024.0118","DOIUrl":"10.3343/alm.2024.0118","url":null,"abstract":"<p><p>The LabGenius C-CT/NG-BMX assay (LabGenius CT/NG; BIOMEDUX, Gyeonggi, Republic of Korea) is a recently developed real-time PCR assay that can simultaneously detect the sexually transmitted pathogens <i>Chlamydia trachomatis</i> (CT) and <i>Neisseria gonorrhoeae</i> (NG) in genitourinary specimens. We evaluated the analytical performance of this assay in comparison with BD MAX CT/GC/TV (Becton Dickinson, Franklin Lakes, NJ, USA). The results of both assays were in nearly perfect agreement for the detection of CT and NG. LabGenius CT/NG demonstrated acceptable analytical performance, comparable with that of another commercially available kit, and provides a cost-effective option for detecting sexually transmitted pathogens in routine and follow-up testing.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"218-222"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Machine Learning Approach for Predicting In-Hospital Cardiac Arrest Using Single-Day Vital Signs, Laboratory Test Results, and International Classification of Disease-10 Block for Diagnosis.","authors":"Haeil Park, Chan Seok Park","doi":"10.3343/alm.2024.0315","DOIUrl":"10.3343/alm.2024.0315","url":null,"abstract":"<p><strong>Background: </strong>Predicting in-hospital cardiac arrest (IHCA) is crucial for potentially reducing mortality and improving patient outcomes. However, most models, which rely solely on vital signs, may not comprehensively capture the patients' risk profiles. We aimed to improve IHCA predictions by combining vital sign indicators with laboratory test results and, optionally, International Classification of Disease-10 block for diagnosis (ICD10BD).</p><p><strong>Methods: </strong>We conducted a retrospective cohort study in the general ward (GW) and intensive care unit (ICU) of a 680-bed secondary healthcare institution. We included 62,061 adults admitted to the Department of Internal Medicine from January 2010 to August 2022. IHCAs were identified based on cardiopulmonary resuscitation prescriptions. Patient-days within three days preceding IHCAs were labeled as case days; all others were control days. The eXtreme Gradient Boosting (XGBoost) model was trained using daily vital signs, 14 laboratory test results, and ICD10BD.</p><p><strong>Results: </strong>In the GW, among 1,299,448 patient-days from 62,038 patients, 1,367 days linked to 713 patients were cases. In the ICU, among 117,190 patient-days from 16,881 patients, 1,119 days from 444 patients were cases. The area under the ROC curve for IHCA prediction model was 0.934 and 0.896 in the GW and ICU, respectively, using the combination of vital signs, laboratory test results, and ICD10BD; 0.925 and 0.878, respectively, with vital signs and laboratory test results; and 0.839 and 0.828, respectively, with only vital signs.</p><p><strong>Conclusions: </strong>Incorporating laboratory test results or combining laboratory test results and ICD10BD with vital signs as predictor variables in the XGBoost model potentially enhances clinical decision-making and improves patient outcomes in hospital settings.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"209-217"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>TP53</i> Mutation Status in Myelodysplastic Neoplasm and Acute Myeloid Leukemia: Impact of Reclassification Based on the 5th WHO and International Consensus Classification Criteria: A Korean Multicenter Study.","authors":"Hyun-Young Kim, Saeam Shin, Jong-Mi Lee, In-Suk Kim, Boram Kim, Hee-Jin Kim, Yu Jeong Choi, Byunggyu Bae, Yonggoo Kim, Eunhui Ji, Hyerin Kim, Hyerim Kim, Jee-Soo Lee, Yoon Hwan Chang, Hyun Kyung Kim, Ja Young Lee, Shinae Yu, Miyoung Kim, Young-Uk Cho, Seongsoo Jang, Myungshin Kim","doi":"10.3343/alm.2024.0351","DOIUrl":"10.3343/alm.2024.0351","url":null,"abstract":"<p><strong>Background: </strong><i>TP53</i> mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize <i>TP53</i>-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of <i>TP53</i>-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications.</p><p><strong>Methods: </strong>This study included patients aged ≥ 18 yrs who were diagnosed as having MDS (N=1,244) or AML (N=2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including <i>TP53</i>, were collected and analyzed.</p><p><strong>Results: </strong><i>TP53</i> mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/R273/G245/Y220/R175/C238 accounting for 25.4% of <i>TP53</i> mutations. Ten percent of patients had multiple <i>TP53</i> mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of <i>TP53</i> mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit <i>TP53</i> mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a <i>TP53</i> VAF >50% for the 5th WHO classification and the presence of a complex karyotype for the ICC.</p><p><strong>Conclusions: </strong>Collectively, we elucidated the molecular genetic characteristics of patients with <i>TP53</i>-mutated MDS and AML, highlighting key factors in applying <i>TP53</i> mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"160-169"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Value of Residual Circulating Tumor DNA in Metastatic Pancreatic Ductal Adenocarcinoma.","authors":"Hongkyung Kim, Jinho Lee, Mi Ri Park, Zisun Choi, Seung Jung Han, Dongha Kim, Saeam Shin, Seung-Tae Lee, Jong Rak Choi, Seung Woo Park","doi":"10.3343/alm.2024.0345","DOIUrl":"10.3343/alm.2024.0345","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumor DNA (ctDNA) is a potential biomarker in pancreatic ductal adenocarcinoma (PDAC). However, studies on residual ctDNA in patients post-chemotherapy are limited. We assessed the prognostic value of residual ctDNA in metastatic PDAC relative to that of carbohydrate antigen 19-9 (CA19-9).</p><p><strong>Methods: </strong>ctDNA analysis using a targeted next-generation sequencing panel was performed at baseline and during chemotherapy response evaluation in 53 patients. Progression-free survival (PFS) and overall survival (OS) were first evaluated based on ctDNA positivity at baseline. For further comparison, patients testing ctDNA-positive at baseline were subdivided based on residual ctDNA into ctDNA responders (no residual ctDNA post-chemotherapy) and ctDNA non-responders (residual ctDNA post-chemotherapy). Additional survival analysis was performed based on CA19-9 levels.</p><p><strong>Results: </strong>The baseline ctDNA detection rate was 56.6%. Although clinical outcomes tended to be poorer in patients with baseline ctDNA positivity than in those without, the differences were not significant. Residual ctDNA post-chemotherapy was associated with reduced PFS and OS. The prognosis of ctDNA responders was better than that of non-responders but did not significantly differ from that of ctDNA-negative individuals (no ctDNA both at baseline and during post-chemotherapy). Compared with ctDNA responses to chemotherapy, a ≥ 50% decrease in the CA19-9 level had less effect on both PFS and OS based on hazard ratios and significance levels. ctDNA could be monitored in half of the patients whose baseline CA19-9 levels were within the reference range.</p><p><strong>Conclusions: </strong>Residual ctDNA analysis post-chemotherapy is a promising approach for predicting the clinical outcomes of patients with metastatic PDAC.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"199-208"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reclassification of Acute Myeloid Leukemia According to the 2022 World Health Organization Classification and the International Consensus Classification Using Open-Source Data.","authors":"Jiwon Yun","doi":"10.3343/alm.2024.0194","DOIUrl":"10.3343/alm.2024.0194","url":null,"abstract":"<p><strong>Background: </strong>In 2022, the revised WHO classification and International Consensus Classification (ICC) for myeloid neoplasms were published. We examined the impact of these guidelines on AML diagnoses alongside the 2022 European LeukemiaNet (ELN) recommendations on risk stratification.</p><p><strong>Methods: </strong>We included 450 adult patients with newly diagnosed AML (non-acute promyelocytic leukemia) from the cBioPortal open-source dataset. Diagnoses and risk stratifications were revised based on the new guidelines and compared with the 2017 WHO classification. Survival analyses were performed using Cox regression.</p><p><strong>Results: </strong>Among the patients included, 190 (42.2%) had consistent diagnoses across the three classifications, whereas 225 (50.0%) had inconsistent diagnoses. The two major WHO 2017 subtypes, AML not otherwise specified (AML-NOS) and AML with myelodysplasia-related changes (AML-MRC), were further subdivided according to the WHO 2022 and ICC. The ICC had the highest prognostication power among the three classifications. Subgroup analysis according to the different definitions of myelodysplasia-related AML and the introduction of AML with mutated TP53 (AML-<i>TP53</i>) showed that the differentiation of AML-<i>TP53</i> was beneficial. The update from ELN 2017 to ELN 2022 resulted in significant transitions in a subset of patients. The updated diagnostic classification and ELN risk stratification (i.e., the ICC and ELN 2022) showed a straightforward relationship.</p><p><strong>Conclusions: </strong>This study presents an integrative comparative analysis of past and current guidelines for AML diagnosis and risk classification based on open-source data. The ICC diagnostic criteria are clinically significant for determining AML prognosis. In line with the changing treatment paradigm for AML, future research is needed to continuously validate diagnostic and risk stratification systems.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"170-177"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD69 Expression is Negatively Associated With T-Cell Immunity and Predicts Antiviral Therapy Response in Chronic Hepatitis B.","authors":"Yurong Gu, Yanhua Bi, Zexuan Huang, Chunhong Liao, Xiaoyan Li, Hao Hu, Huaping Xie, Yuehua Huang","doi":"10.3343/alm.2024.0178","DOIUrl":"10.3343/alm.2024.0178","url":null,"abstract":"<p><strong>Background: </strong>The function of CD69 expressed on T cells in chronic hepatitis B (CHB) remains unclear. We aimed to elucidate the roles of CD69 on T cells in the disease process and in antiviral therapy for CHB.</p><p><strong>Methods: </strong>We enrolled 335 treatment-naive patients with CHB and 93 patients with CHB on antiviral therapy. CD69, antiviral cytokine production by T cells, T-helper (Th) cells, and inhibitory molecules of T cells were measured using flow cytometry, and clinical-virological characteristics were examined dynamically during antiviral therapy.</p><p><strong>Results: </strong>CD69 expression on CD3+, CD4+, and CD8+ T cells was the lowest in the immune-active phase and was negatively correlated with liver transaminase activity, fibrosis features, inflammatory cytokine production by T cells, and Th-cell frequencies but positively with inhibitory molecules on T cells. CD69 expression on CD3+, CD4+, and CD8+ T cells decreased after 48 weeks of antiviral therapy, and patients with hepatitis B e antigen (HBeAg) seroconversion in week 48 showed lower CD69 expression on T cells at baseline and week 48. The area under the ROC curve of CD69 expression on T cells at baseline for predicting HBeAg seroconversion in week 48 was 0.870, the sensitivity was 0.909, and the specificity was 0.714 (<i>P</i> =0.002).</p><p><strong>Conclusions: </strong>CD69 negatively regulates T-cell immunity during CHB, and its expression decreases with antiviral therapy. CD69 expression predicts HBeAg seroconversion in week 48. CD69 may play an important negative role in regulating T cells and affect the efficacy of antiviral therapy.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"185-198"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Pharmacogenetic Testing and Application: 2024 Updated Guidelines by the Korean Society for Laboratory Medicine.","authors":"John Hoon Rim, Young-Gon Kim, Sollip Kim, Rihwa Choi, Jee-Soo Lee, Seungman Park, Woochang Lee, Eun Young Song, Soo-Youn Lee, Sail Chun","doi":"10.3343/alm.2024.0572","DOIUrl":"10.3343/alm.2024.0572","url":null,"abstract":"<p><p>In the era of precision medicine, pharmacogenetics has substantial potential for addressing inter-individual variability in drug responses. Although pharmacogenetics has been a research focus for many years, resulting in the establishment of several formal guidelines, its clinical implementation remains limited to several gene-drug combinations in most countries, including Korea. The main causes of delayed implementation are technical challenges in genotyping and knowledge gaps among healthcare providers; therefore, clinical laboratories play a critical role in the timely implementation of pharmacogenetics. This paper presents an update of the Clinical Pharmacogenetic Testing and Application guidelines issued by the Korean Society for Laboratory Medicine and aims to provide the necessary information for clinical laboratories planning to implement or expand their pharmacogenetic testing. Current knowledge regarding nomenclature, gene-drug relationships, genotyping technologies, testing strategies, methods for clinically relevant information delivery, QC, and reimbursements has been curated and described in this guideline.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"121-132"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Relevance of Non-molecular Prognostic Systems for Myelodysplastic Syndrome in the Era of Next-Generation Sequencing.","authors":"Marco Lincango, Verónica Andreoli, Hernán García Rivello, Andrea Bender, Ana I Catalán, Marilina Rahhal, Rocío Delamer, Mariana Asinari, Adrián Mosquera Orgueira, María Belén Castro, María José Mela Osorio, Alicia Navickas, Sofia Grille, Evangelina Agriello, Jorge Arbelbide, Ana Lisa Basquiera, Carolina B Belli","doi":"10.3343/alm.2024.0089","DOIUrl":"10.3343/alm.2024.0089","url":null,"abstract":"<p><strong>Background: </strong>The Molecular International Prognostic Scoring System (IPSS-M) has improved the prediction of clinical outcomes for myelodysplastic syndromes (MDS). The Artificial Intelligence Prognostic Scoring System for MDS (AIPSS-MDS), based on classical clinical parameters, has outperformed the IPSS, revised version (IPSS-R). For the first time, we validated the IPSS-M and other molecular prognostic models and compared them with the established IPSS-R and AIPSS-MDS models using data from South American patients.</p><p><strong>Methods: </strong>Molecular and clinical data from 145 patients with MDS and 37 patients with MDS/myeloproliferative neoplasms were retrospectively analyzed.</p><p><strong>Results: </strong>Prognostic power evaluation revealed that the IPSS-M (Harrell's concordance [C]-index: 0.75, area under the receiver operating characteristic curve [AUC]: 0.68) predicted overall survival better than the European MDS (EuroMDS; C-index: 0.72, AUC: 0.68) and Munich Leukemia Laboratory (MLL) (C-index: 0.70, AUC: 0.64) models. The IPSS-M prognostic discrimination was similar to that of the AIPSS-MDS model (C-index: 0.74, AUC: 0.66) and outperformed the IPSS-R model (C-index: 0.70, AUC: 0.61). Considering simplified low- and high-risk groups for clinical management, after restratifying from IPSS-R (57% and 32%, respectively, hazard ratio [HR]: 2.8; <i>P</i>=0.002) to IPSS-M, 12.6% of patients were upstaged, and 5% were downstaged (HR: 2.9; <i>P</i>=0.001). The AIPSS-MDS recategorized 51% of the low-risk cohort as high-risk, with no patients being downstaged (HR: 5.6; <i>P</i><0.001), consistent with most patients requiring disease-modifying therapy.</p><p><strong>Conclusions: </strong>The IPSS-M and AIPSS-MDS models provide more accurate survival prognoses than the IPSS-R, EuroMDS, and MLL models. The AIPSS-MDS model is a valid option for assessing risks for all patients with MDS, especially in resource-limited centers where molecular testing is not currently a standard clinical practice.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"44-52"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reanalysis of Next-generation Sequencing Data in Patients With Hypertrophic Cardiomyopathy: Contribution of Spliceogenic <i>MYBPC3</i> Variants in an Italian Cohort.","authors":"Silvia Caroselli, Marco Fabiani, Caterina Micolonghi, Camilla Savio, Giacomo Tini, Beatrice Musumeci, Erika Pagannone, Aldo Germani, Fabio Libi, Vincenzo Visco, Antonio Pizzuti, Camillo Autore, Simona Petrucci, Speranza Rubattu, Maria Piane","doi":"10.3343/alm.2024.0201","DOIUrl":"10.3343/alm.2024.0201","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is a genetic cardiac muscle disease characterized by clinical and genetic heterogeneity. Genetic testing can reveal the presence of disease-causing variants in genes encoding sarcomere proteins. However, it yields inconclusive or negative results in 40-60% of HCM cases, owing to, among other causes, technical limitations such as the inability to detect pathogenic intronic variants. Therefore, we aimed to increase the diagnostic yield of molecular analysis for HCM by improving the <i>in-silico</i> detection of intronic variants in <i>MYBPC3</i> that may escape detection by algorithms normally used with tagged diagnostic panels. We included 142 HCM probands with negative results in Illumina TruSight Cardio panel analysis, including exonic regions of 174 cardiomyopathy genes. Raw data were re-analyzed using existing bioinformatics tools. The spliceogenic variant c.1224-80G>A was detected in three patients (2.1%), leading us to reconsider their molecular diagnosis. These patients showed late onset and mild symptoms, although no peculiar phenotypic characteristics were shared. Collectively, rare spliceogenic <i>MYBPC3</i> variants may play a role in causing HCM, and their systematic detection should be performed to provide more comprehensive solutions in genetic testing using multigenic panels.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"96-100"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}