Journal of Molecular Diagnostics最新文献_第8页

Strategic Implementation of Fragile X Carrier Screening in China 中国脆性 X 携带者筛查的战略实施：重点试点研究。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-19 DOI: 10.1016/j.jmoldx.2024.06.005

Jin Xue , Yingbao Zhu , Yi Pan , Hongjing Huang , Liyi Wei , Ying Peng , Hui Xi , Shihao Zhou , Hongliang Wu , Zhenxiang Gu , Wen Huang , Hua Wang , Ranhui Duan

{"title":"Strategic Implementation of Fragile X Carrier Screening in China","authors":"Jin Xue , Yingbao Zhu , Yi Pan , Hongjing Huang , Liyi Wei , Ying Peng , Hui Xi , Shihao Zhou , Hongliang Wu , Zhenxiang Gu , Wen Huang , Hua Wang , Ranhui Duan","doi":"10.1016/j.jmoldx.2024.06.005","DOIUrl":"10.1016/j.jmoldx.2024.06.005","url":null,"abstract":"<div><p>Fragile X syndrome is the leading genetic cause of intellectual disability and autism spectrum disorders. Female premutation carriers exhibit no obvious symptoms during reproductive age, but the premutation allele can expand to full mutation when transmitted to the fetus. Given the relatively low prevalence but large population, the distinct health care system, the middle-income economic status, and low awareness among public and medical professionals, the optimal genetic screening strategy remains unknown. We conducted a pilot study of Fragile X carrier screening in China, involving 22,245 pregnant women and women with childbearing intentions, divided into control and pilot groups. The prevalence of Fragile X carriers in the control group was 1 of 850, similar to East Asian populations. Strikingly, the prevalence of Fragile X carriers in the pilot group was 1 of 356, which can be attributed to extensive medical training, participant education, and rigorous genetic counseling and testing protocols. Cost-effectiveness analyses of four strategies—no screening, population-based screening, targeted screening, and our pilot screening—indicated that our pilot screening was the most cost-effective option. A follow-up survey revealed that 55% of respondents reported undergoing screening because of their family history. We have successfully established a standardized system, addressing the challenges of low prevalence, limited awareness, and genetic testing complexities. Our study provides practical recommendations for implementing Fragile X carrier screening in China.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 10","pages":"Pages 897-905"},"PeriodicalIF":3.4,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DPYD Genotyping Recommendations DPYD 基因分型建议：分子病理学协会、美国医学遗传学和基因组学学院、临床药物遗传学实施联合会、美国病理学家学会、荷兰皇家药剂师协会荷兰药物遗传学工作组、欧洲药物基因组学和个性化治疗学会、药物基因组学知识库和药物基因变异联合会的联合共识建议。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-18 DOI: 10.1016/j.jmoldx.2024.05.015

Victoria M. Pratt , Larisa H. Cavallari , Makenzie L. Fulmer , Andrea Gaedigk , Houda Hachad , Yuan Ji , Lisa V. Kalman , Reynold C. Ly , Ann M. Moyer , Stuart A. Scott , Amy J. Turner , Ron H.N. van Schaik , Michelle Whirl-Carrillo , Karen E. Weck

{"title":"DPYD Genotyping Recommendations","authors":"Victoria M. Pratt , Larisa H. Cavallari , Makenzie L. Fulmer , Andrea Gaedigk , Houda Hachad , Yuan Ji , Lisa V. Kalman , Reynold C. Ly , Ann M. Moyer , Stuart A. Scott , Amy J. Turner , Ron H.N. van Schaik , Michelle Whirl-Carrillo , Karen E. Weck","doi":"10.1016/j.jmoldx.2024.05.015","DOIUrl":"10.1016/j.jmoldx.2024.05.015","url":null,"abstract":"<div><p>The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations for a minimum set of variant alleles (tier 1) and an extended list of variant alleles (tier 2) that will aid clinical laboratories when designing assays for PGx testing. The Association for Molecular Pathology PGx Working Group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. The goal of this Working Group is to promote standardization of PGx testing across clinical laboratories. This document will focus on clinical <em>DPYD</em> PGx testing that may be applied to all dihydropyrimidine dehydrogenase–related medications. These recommendations are not to be interpreted as prescriptive but to provide a reference guide.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 10","pages":"Pages 851-863"},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001545/pdfft?md5=e0bda1c43cd5d77f5cf6e9737bd1ec28&pid=1-s2.0-S1525157824001545-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multisite Evaluation and Validation of Optical Genome Mapping for Prenatal Genetic Testing 用于产前基因检测的光学基因组图谱的多点评估和验证。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-18 DOI: 10.1016/j.jmoldx.2024.06.006

Brynn Levy , Jie Liu , M. Anwar Iqbal , Barbara DuPont , Nikhil Sahajpal , Monique Ho , Jingwei Yu , Sam J. Brody , Mythily Ganapathi , Aleksandar Rajkovic , Teresa A. Smolarek , Fatih Boyar , Peter Bui , Adrian M. Dubuc , Ravindra Kolhe , Roger E. Stevenson

{"title":"Multisite Evaluation and Validation of Optical Genome Mapping for Prenatal Genetic Testing","authors":"Brynn Levy , Jie Liu , M. Anwar Iqbal , Barbara DuPont , Nikhil Sahajpal , Monique Ho , Jingwei Yu , Sam J. Brody , Mythily Ganapathi , Aleksandar Rajkovic , Teresa A. Smolarek , Fatih Boyar , Peter Bui , Adrian M. Dubuc , Ravindra Kolhe , Roger E. Stevenson","doi":"10.1016/j.jmoldx.2024.06.006","DOIUrl":"10.1016/j.jmoldx.2024.06.006","url":null,"abstract":"<div><p>Prenatal diagnostic testing of amniotic fluid, chorionic villi, or more rarely, fetal cord blood is recommended following a positive or unreportable noninvasive cell-free fetal DNA test, abnormal maternal biochemical serum screen, abnormal ultrasound, or increased genetic risk for a cytogenomic abnormality based on family history. Although chromosomal microarray is recommended as the first-tier prenatal diagnostic test, in practice, multiple assays are often assessed in concert to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping (OGM) is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenomic aberrations. In an effort to characterize the potential of OGM as a novel alternative to traditional standard of care (SOC) testing of prenatal samples, OGM was performed on a total of 200 samples representing 123 unique cases, which were previously tested with SOC methods (92/123 = 74.7% cases tested with at least two SOCs). OGM demonstrated an overall accuracy of 99.6% when compared with SOC methods, a positive predictive value of 100%, and 100% reproducibility between sites, operators, and instruments. The standardized workflow, cost-effectiveness, and high-resolution cytogenomic analysis demonstrate the potential of OGM to serve as a first-tier test for prenatal diagnosis.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 10","pages":"Pages 906-916"},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001570/pdfft?md5=5bf6d88f32dd52ed0a19de6229f626d7&pid=1-s2.0-S1525157824001570-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of Reference Materials for DPYD DPYD 参考材料的表征：GeT-RM 合作项目。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-18 DOI: 10.1016/j.jmoldx.2024.06.004

Andrea Gaedigk , Amy J. Turner , Ann M. Moyer , Pablo Zubiaur , Erin C. Boone , Wendy Y. Wang , Ulrich Broeckel , Lisa V. Kalman

{"title":"Characterization of Reference Materials for DPYD","authors":"Andrea Gaedigk , Amy J. Turner , Ann M. Moyer , Pablo Zubiaur , Erin C. Boone , Wendy Y. Wang , Ulrich Broeckel , Lisa V. Kalman","doi":"10.1016/j.jmoldx.2024.06.004","DOIUrl":"10.1016/j.jmoldx.2024.06.004","url":null,"abstract":"<div><p>The <em>DPYD</em> gene encodes dihydropyrimidine dehydrogenase (DPD), which is involved in the catalysis of uracil and thymine, as well as 5-fluorouracil (5-FU), which is used to treat solid tumors. Patients with decreased DPD activity are at risk of serious, sometimes fatal, adverse drug reactions to this important cancer drug. Pharmacogenetic testing for <em>DPYD</em> is increasingly provided by clinical and research laboratories; however, only a limited number of quality control and reference materials are currently available for clinical <em>DPYD</em> testing. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention–based Genetic Testing Reference Materials Coordination Program, in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 33 DNA samples derived from Coriell cell lines for <em>DPYD</em>. Samples were distributed to four volunteer laboratories for genetic testing using a variety of commercially available and laboratory-developed tests. Sanger sequencing was used by one laboratory and publicly available whole-genome sequence data from the 1000 Genomes Project were used by another to inform genotype. Thirty-three distinct <em>DPYD</em> variants were identified among the 33 samples characterized. These publicly available and well-characterized materials can be used to support the quality assurance and quality control programs of clinical laboratories performing clinical pharmacogenetic testing.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 10","pages":"Pages 864-875"},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Validation and Implementation of a Somatic-Only Tumor Exome for Routine Clinical Application 用于常规临床应用的体细胞肿瘤外显子组的验证和实施。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-06 DOI: 10.1016/j.jmoldx.2024.05.013

引用次数: 0

Assessing the Risk Stratification of Breast Cancer Polygenic Risk Scores in a Brazilian Cohort 评估巴西队列中乳腺癌多基因风险评分的风险分层。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-06 DOI: 10.1016/j.jmoldx.2024.06.002

{"title":"Assessing the Risk Stratification of Breast Cancer Polygenic Risk Scores in a Brazilian Cohort","authors":"","doi":"10.1016/j.jmoldx.2024.06.002","DOIUrl":"10.1016/j.jmoldx.2024.06.002","url":null,"abstract":"<div><p>Polygenic risk scores (PRSs) for breast cancer have a clear clinical utility in risk prediction. PRS transferability across populations and ancestry groups is hampered by population-specific factors, ultimately leading to differences in variant effects, such as linkage disequilibrium and differences in variant frequency (allele frequency differences). Thus, locally sourced population-based phenotypic and genomic data sets are essential to assess the validity of PRSs derived from signals detected across populations. This study assesses the transferability of a breast cancer PRS composed of 313 risk variants (313-PRS) in a Brazilian trihybrid admixed ancestries (European, African, and Native American) whole-genome sequenced cohort, the Rare Genomes Project. 313-PRS was computed in the Rare Genomes Project (<em>n</em> = 853) using the UK Biobank (UKBB; <em>n</em> = 264,307) as reference. The Brazilian cohorts have a high European ancestry (EA) component, with allele frequency differences and to a lesser extent linkage disequilibrium patterns similar to those found in EA populations. The 313-PRS distribution was found to be inflated when compared with that of the UKBB, leading to potential overestimation of PRS-based risk if EA is taken as a standard. However, case controls lead to equivalent predictive power when compared with UKBB-EA samples with area under the receiver operating characteristic curve values of 0.66 to 0.62 compared with 0.63 for UKBB.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 9","pages":"Pages 825-831"},"PeriodicalIF":3.4,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Utility of Real-Time PCR, Metagenomic Next-Generation Sequencing, and Culture in Bronchoalveolar Lavage Fluid for Diagnosis of Pulmonary Aspergillosis 实时 PCR、元基因组新一代测序和支气管肺泡灌洗液培养在诊断肺曲霉菌病中的实用性。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-06 DOI: 10.1016/j.jmoldx.2024.06.003

{"title":"The Utility of Real-Time PCR, Metagenomic Next-Generation Sequencing, and Culture in Bronchoalveolar Lavage Fluid for Diagnosis of Pulmonary Aspergillosis","authors":"","doi":"10.1016/j.jmoldx.2024.06.003","DOIUrl":"10.1016/j.jmoldx.2024.06.003","url":null,"abstract":"<div><p>Timely detection of <em>Aspergillus</em> infection is crucial given the high mortality rate of pulmonary aspergillosis (PA). Here, the diagnostic performances for PA of mycological culture, <em>Aspergillus</em> real-time PCR, and metagenomic next-generation sequencing (mNGS) assay from bronchoalveolar lavage fluid, were evaluated. In total, 139 patients with suspected fungal pneumonia were enrolled between December 2021 and July 2023, collecting 139 bronchoalveolar lavage fluid samples for real-time PCR and culture, with 87 undergoing mNGS assay. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve with 95% CIs of these assays for PA were as follows: 35.3% (14.2%–61.7%), 100.0% (94.0%–100.0%), 100.0% (54.1%–100.0%), 84.5% (79.3%–88.6%), and 0.676 (0.560–0.779), respectively, for culture; 82.4% (56.6%–96.2%), 98.3% (91.1%–100.0%), 93.3% (66.4%–99.0%), 95.2% (87.6%–98.2%), and 0.903 (0.815–0.959), respectively, for same diagnostic performance of real-time PCR and mNGS; and 94.1% (71.3%–99.9%), 96.7% (88.5%–99.6%), 88.9% (67.1%–96.9%), 98.3% (89.6%–99.7%), and 0.954 (0.880–0.989), respectively, for real-time PCR combining mNGS; real-time PCR, mNGS, and their combination significantly improved in area under the curve values over culture (<em>P</em> < 0.001), but real-time PCR testing and mNGS had no significant difference with each other and their combination. Overall, the performance of culture was limited by low sensitivity; both real-time PCR and mNGS assays as single diagnostic tests are promising compared with culture and combined tests.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 9","pages":"Pages 832-842"},"PeriodicalIF":3.4,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development, Validation, and Implementation of an Augmented Multiwell, Multitarget Quantitative PCR for the Analysis of Human Papillomavirus Genotyping through Software Automation, Data Science, and Artificial Intelligence 通过软件自动化、数据科学和人工智能，开发、验证和实施增强型多孔、多靶点定量 PCR-HPV 基因分型分析。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-05 DOI: 10.1016/j.jmoldx.2024.05.012

{"title":"Development, Validation, and Implementation of an Augmented Multiwell, Multitarget Quantitative PCR for the Analysis of Human Papillomavirus Genotyping through Software Automation, Data Science, and Artificial Intelligence","authors":"","doi":"10.1016/j.jmoldx.2024.05.012","DOIUrl":"10.1016/j.jmoldx.2024.05.012","url":null,"abstract":"<div><p>The value of human papillomavirus (HPV) testing for cervical cancer screening is well established; however, its use as a primary screening option or as a reflex test after atypical cytology results is now gaining wider acceptance. The importance of full genotyping and viral load determination has been demonstrated to enhance the clinical understanding of the viral infection progression during follow-up or after treatment, thereby providing clinicians with supplementary tools for optimized patient management. We developed a new analysis method for the RIATOL quantitative PCR assay, and validated and implemented it in the laboratory of clinical molecular pathology at Algemeen Medisch Laboratorium (AML), under national accreditation and following the International Organization for Standardization guidelines. This study presents the successful validation of a high-throughput, multitarget HPV analysis method, with enhanced accuracy on both qualitative and quantitative end results. This is achieved by software standardization and automation of PCR curve analysis and interpretation, using data science and artificial intelligence. Moreover, the user-centric functionality of the platform was demonstrated to enhance both staff training and routine analysis workflows, thereby saving time and laboratory personnel resources. Overall, the integration of the FastFinder plugin semi-automatic analysis algorithm with the RIATOL real-time quantitative PCR assay proved to be a remarkable advancement in high-throughput HPV quantification, with demonstrated capability to provide highly accurate clinical-grade results and to reduce manual variability and analysis time.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 9","pages":"Pages 781-791"},"PeriodicalIF":3.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001491/pdfft?md5=2946f126a90ecf1d060162a13b5d0172&pid=1-s2.0-S1525157824001491-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma Protein Profiling to Discern Indolent from Advanced Systemic Mastocytosis 通过血浆蛋白图谱分析鉴别轻度和晚期系统性肥大细胞增多症。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-06-24 DOI: 10.1016/j.jmoldx.2024.05.010

{"title":"Plasma Protein Profiling to Discern Indolent from Advanced Systemic Mastocytosis","authors":"","doi":"10.1016/j.jmoldx.2024.05.010","DOIUrl":"10.1016/j.jmoldx.2024.05.010","url":null,"abstract":"<div><p>Mastocytosis is a heterogeneous disorder characterized by abnormal mast cell accumulation, in which the clinical severity may be explained by distinct molecular mechanisms. This study aimed to explore plasma protein biomarkers associated with systemic mastocytosis subtypes, as well as the cellular origin of the identified proteins. Plasma samples from patients with mastocytosis, including cutaneous mastocytosis (CM), indolent systemic mastocytosis (ISM), and advanced systemic mastocytosis (AdvSM), and a reference group of patients with polycythemia vera, were analyzed by Proximity Extension Assay technology targeting 275 proteins. Furthermore, potential cellular origin was explored using an available single-cell RNA-sequencing data set generated from patients with ISM. The study cohort included 16 patients with CM, 92 patients with systemic mastocytosis (ISM, <em>n</em> = 80; AdvSM, <em>n</em> = 12), and 60 patients with polycythemia vera. A principal component analysis based on 275 plasma proteins revealed one cluster of patients with CM and ISM that was separated from patients with AdvSM. Up to 29 proteins were associated with distinct severe activity in patients with systemic mastocytosis (ISM versus AdvSM), including IL-1 receptor type 1 (IL-1RT1) and tumor necrosis factor ligand superfamily member 13B (TNFSF13B) (q < 0.01). Furthermore, single-cell RNA-sequencing analysis from ISM-derived bone marrow cells revealed that the mRNA for the identified proteins was not exclusive of mast cells. Distinct plasma protein profiles show potential to refine ISM and AdvSM diagnoses, possibly reflecting differences in pathogenic mechanisms and diverse clinical manifestations.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 9","pages":"Pages 792-804"},"PeriodicalIF":3.4,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001302/pdfft?md5=4cb224273eb6f37b9dc06a280845239e&pid=1-s2.0-S1525157824001302-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improved Genetic Characterization of Congenital Adrenal Hyperplasia by Long-Read Sequencing Compared with Multiplex Ligation-Dependent Probe Amplification Plus Sanger Sequencing 与多重连接依赖性探针扩增加桑格测序法相比，长线程测序法改进了先天性肾上腺增生症的遗传特征描述。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-06-24 DOI: 10.1016/j.jmoldx.2024.05.009

{"title":"Improved Genetic Characterization of Congenital Adrenal Hyperplasia by Long-Read Sequencing Compared with Multiplex Ligation-Dependent Probe Amplification Plus Sanger Sequencing","authors":"","doi":"10.1016/j.jmoldx.2024.05.009","DOIUrl":"10.1016/j.jmoldx.2024.05.009","url":null,"abstract":"<div><p>Genetic analysis of congenital adrenal hyperplasia (CAH) has been challenging because of high homology between <em>CYP21A2</em> and its pseudogene <em>CYP21A1P</em>. This study aimed to evaluate the clinical utility of long-read sequencing (LRS) in diagnosis of CAH attributable to 21-hydroxylase deficiency by comparing with multiplex ligation-dependent probe amplification plus Sanger sequencing. In this retrospective study, 69 samples, including 49 probands from 47 families with high-risk of CAH, were enrolled and blindly subjected to detection of CAH by LRS. The genotype results were compared with control methods, and discordant samples were validated by additional Sanger sequencing. LRS successfully identified biallelic variants of <em>CYP21A2</em> in the 39 probands diagnosed as having CAH. The remaining 10 probands were not patients with CAH. Additionally, LRS directly identified two pathogenic single-nucleotide variations (SNVs; c.293-13C/A>G and c.955C>T) in the presence of interference caused by nearby insertions/deletions (indels). The <em>cis</em>-<em>trans</em> configuration of two or more SNVs and indels identified in 18 samples was directly determined by LRS without family analysis. Eight <em>CYP21A1P/A2</em> or <em>TNXA/B</em> deletion chimeras, composed of five subtypes, were identified; and the junction sites were precisely determined. Moreover, LRS determined the exact genotype in two probands who had three heterozygous SNVs/indels and duplication, which could not be clarified by control methods. These findings highlight that LRS could assist in more accurate genotype imputation and more precise CAH diagnosis.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 9","pages":"Pages 770-780"},"PeriodicalIF":3.4,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001296/pdfft?md5=97afdb5a234db4132211f866324c16d0&pid=1-s2.0-S1525157824001296-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0