首页 > 最新文献

Human Heredity最新文献

英文 中文
51st European Mathematical Genetics Meeting (EMGM) 2023. 第 51 届欧洲数学遗传学会议(EMGM)2023。
IF 1.8 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 Epub Date: 2023-12-12 DOI: 10.1159/000535389
Inga Prokopenko, Ayşe Demirkan, Marika Kaakinen

NA.

NA.
{"title":"51st European Mathematical Genetics Meeting (EMGM) 2023.","authors":"Inga Prokopenko, Ayşe Demirkan, Marika Kaakinen","doi":"10.1159/000535389","DOIUrl":"https://doi.org/10.1159/000535389","url":null,"abstract":"<p><p>NA.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Methods and Software to Analyze Gene-Environment Interactions under a Case-Mother-Control-Mother Design with Partially Missing Child Genotype. 分析具有部分缺失儿童基因型的病例-母亲-对照-母亲设计下基因-环境相互作用的方法和软件。
IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-01 Epub Date: 2023-04-26 DOI: 10.1159/000529559
Alexandre Bureau, Yuang Tian, Patrick Levallois, Yves Giguère, Jinbo Chen, Hong Zhang

Introduction: The case-mother-control-mother design allows to study fetal and maternal genetic factors together with environmental exposures on early life outcomes. Mendelian constraints and conditional independence between child genotype and environmental factors enabled semiparametric likelihood methods to estimate logistic models with greater efficiency than standard logistic regression. Difficulties in child genotype collection require methods handling missing child genotype.

Methods: We review a stratified retrospective likelihood and two semiparametric likelihood approaches: a prospective one and a modified retrospective one, the latter either modeling the maternal genotype as a function of covariates or leaving their joint distribution unspecified (robust version). We also review software implementing these modeling alternatives, compare their statistical properties in a simulation study, and illustrate their application, focusing on gene-environment interactions and partially missing child genotype.

Results: The robust retrospective likelihood provides generally unbiased estimates, with standard errors only slightly larger than when modeling maternal genotype based on exposure. The prospective likelihood encounters maximization problems. In the application to the association of small-for-gestational-age babies with CYP2E1 and drinking water disinfection by-products, the retrospective likelihood allowed a full array of covariates, while the prospective likelihood was limited to few covariates.

Conclusion: We recommend the robust version of the modified retrospective likelihood.

简介通过病例-母亲-对照-母亲的设计,可以研究胎儿和母亲的遗传因素以及环境暴露对生命早期结果的影响。儿童基因型与环境因素之间的孟德尔约束和条件独立性使得半参数似然法能够比标准逻辑回归更有效地估计逻辑模型。由于收集儿童基因型存在困难,因此需要处理缺失儿童基因型的方法:我们回顾了一种分层回顾似然法和两种半参数似然法:一种前瞻性似然法和一种改进的回顾性似然法,后者将母体基因型建模为协变量的函数或不指定其联合分布(稳健型)。我们还回顾了实现这些建模方法的软件,在模拟研究中比较了它们的统计特性,并以基因-环境交互作用和部分缺失的儿童基因型为重点,说明了它们的应用:结果:稳健回溯似然法提供的估计值基本无偏,其标准误差仅略大于根据暴露建立母体基因型模型时的标准误差。前瞻性似然法遇到了最大化问题。在应用 CYP2E1 和饮用水消毒副产物与小妊高症婴儿的关系时,回顾性似然法允许使用所有的协变量,而前瞻性似然法仅限于少数几个协变量:结论:我们推荐使用稳健版的改良追溯似然法。
{"title":"Methods and Software to Analyze Gene-Environment Interactions under a Case-Mother-Control-Mother Design with Partially Missing Child Genotype.","authors":"Alexandre Bureau, Yuang Tian, Patrick Levallois, Yves Giguère, Jinbo Chen, Hong Zhang","doi":"10.1159/000529559","DOIUrl":"10.1159/000529559","url":null,"abstract":"<p><strong>Introduction: </strong>The case-mother-control-mother design allows to study fetal and maternal genetic factors together with environmental exposures on early life outcomes. Mendelian constraints and conditional independence between child genotype and environmental factors enabled semiparametric likelihood methods to estimate logistic models with greater efficiency than standard logistic regression. Difficulties in child genotype collection require methods handling missing child genotype.</p><p><strong>Methods: </strong>We review a stratified retrospective likelihood and two semiparametric likelihood approaches: a prospective one and a modified retrospective one, the latter either modeling the maternal genotype as a function of covariates or leaving their joint distribution unspecified (robust version). We also review software implementing these modeling alternatives, compare their statistical properties in a simulation study, and illustrate their application, focusing on gene-environment interactions and partially missing child genotype.</p><p><strong>Results: </strong>The robust retrospective likelihood provides generally unbiased estimates, with standard errors only slightly larger than when modeling maternal genotype based on exposure. The prospective likelihood encounters maximization problems. In the application to the association of small-for-gestational-age babies with CYP2E1 and drinking water disinfection by-products, the retrospective likelihood allowed a full array of covariates, while the prospective likelihood was limited to few covariates.</p><p><strong>Conclusion: </strong>We recommend the robust version of the modified retrospective likelihood.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10308538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9725507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Diagnostic Value of miR-124a Expression in Peripheral Blood and Synovial Fluid of Patients with Rheumatoid Arthritis. 类风湿关节炎患者外周血和滑膜液中 miR-124a 表达的诊断价值
IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-01 Epub Date: 2023-06-14 DOI: 10.1159/000529171
Tianhao Wu, Yanlong Zhang, Aqin Peng, Xirui Wu

Introduction: Rheumatoid arthritis (RA), a chronic autoimmune disorder, is currently a severe health threat. Previous studies have documented the altered expression of various miRNAs in RA patients. This study determined the expression of miR-124a in RA patients and estimated its diagnostic value for RA.

Methods: A total of 80 RA patients were enrolled as the study subjects, and 36 patients with osteoarthritis were included, with another 36 healthy people as the controls. miR-124a expression levels in peripheral blood plasma, peripheral blood mononuclear cells (PBMCs), and synovial fluid were measured using reverse transcription quantitative polymerase chain reaction, followed by Pearson correlation analysis. Additionally, the association between miR-124a and major clinical indicators was assessed, such as rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and disease activity score of 28 joints (DAS28). The diagnostic efficacy of miR-124a expression in plasma, PBMCs, and synovial fluid for RA was evaluated by the receiver operating characteristic curve, and the difference in the area under the curve (AUC) was analyzed.

Results: miR-124a was downregulated in RA patients, and the expression levels of miR-124a in plasma, PBMCs, and synovial fluid showed a certain degree of positive correlation. miR-124a was inversely linked with RF, ESR, and DAS28. For the diagnosis of RA patients, the AUC of plasma miR-124a was 0.899 and the cut-off value was 0.800, with 68.75% sensitivity and 94.44% specificity; the AUC of miR-124a in PBMCs was 0.937 and the cut-off value was 0.805, with 82.50% sensitivity and 91.67% specificity; the AUC of miR-124a in plasma combined with PBMCs was 0.961, with a higher diagnostic value than independent plasma or PBMCs; the AUC of miR-124a in synovial fluid was 0.929 and the cut-off value was 0.835, with 80.00% sensitivity and 88.89% specificity.

Conclusion: miR-124a expression is downregulated in the plasma, PBMCs, and synovial fluid of RA patients and has a high diagnostic value for RA.

导言:类风湿性关节炎(RA)是一种慢性自身免疫性疾病,目前正严重威胁着人们的健康。以往的研究记录了各种 miRNA 在 RA 患者中的表达变化。本研究测定了 miR-124a 在 RA 患者中的表达,并估计了其对 RA 的诊断价值:采用反转录定量聚合酶链反应法测定外周血血浆、外周血单核细胞(PBMCs)和滑膜液中 miR-124a 的表达水平,然后进行皮尔逊相关分析。此外,还评估了 miR-124a 与类风湿因子(RF)、红细胞沉降率(ESR)和 28 个关节的疾病活动度评分(DAS28)等主要临床指标之间的关联。结果:miR-124a在RA患者中下调,miR-124a在血浆、PBMCs和滑膜液中的表达水平呈一定程度的正相关,miR-124a与RF、ESR和DAS28成反比。对于 RA 患者的诊断,血浆中 miR-124a 的 AUC 为 0.899,临界值为 0.800,灵敏度为 68.75%,特异度为 94.44%;PBMCs 中 miR-124a 的 AUC 为 0.937,临界值为 0.805,灵敏度为 82.50%,特异度为 91.67%;血浆联合 PBMCs 中 miR-124a 的 AUC 为 0.961,诊断价值高于独立血浆或PBMCs;滑膜液中miR-124a的AUC为0.929,临界值为0.835,敏感性为80.00%,特异性为88.89%。结论:miR-124a在RA患者的血浆、PBMCs和滑膜液中表达下调,对RA具有较高的诊断价值。
{"title":"The Diagnostic Value of miR-124a Expression in Peripheral Blood and Synovial Fluid of Patients with Rheumatoid Arthritis.","authors":"Tianhao Wu, Yanlong Zhang, Aqin Peng, Xirui Wu","doi":"10.1159/000529171","DOIUrl":"10.1159/000529171","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid arthritis (RA), a chronic autoimmune disorder, is currently a severe health threat. Previous studies have documented the altered expression of various miRNAs in RA patients. This study determined the expression of miR-124a in RA patients and estimated its diagnostic value for RA.</p><p><strong>Methods: </strong>A total of 80 RA patients were enrolled as the study subjects, and 36 patients with osteoarthritis were included, with another 36 healthy people as the controls. miR-124a expression levels in peripheral blood plasma, peripheral blood mononuclear cells (PBMCs), and synovial fluid were measured using reverse transcription quantitative polymerase chain reaction, followed by Pearson correlation analysis. Additionally, the association between miR-124a and major clinical indicators was assessed, such as rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and disease activity score of 28 joints (DAS28). The diagnostic efficacy of miR-124a expression in plasma, PBMCs, and synovial fluid for RA was evaluated by the receiver operating characteristic curve, and the difference in the area under the curve (AUC) was analyzed.</p><p><strong>Results: </strong>miR-124a was downregulated in RA patients, and the expression levels of miR-124a in plasma, PBMCs, and synovial fluid showed a certain degree of positive correlation. miR-124a was inversely linked with RF, ESR, and DAS28. For the diagnosis of RA patients, the AUC of plasma miR-124a was 0.899 and the cut-off value was 0.800, with 68.75% sensitivity and 94.44% specificity; the AUC of miR-124a in PBMCs was 0.937 and the cut-off value was 0.805, with 82.50% sensitivity and 91.67% specificity; the AUC of miR-124a in plasma combined with PBMCs was 0.961, with a higher diagnostic value than independent plasma or PBMCs; the AUC of miR-124a in synovial fluid was 0.929 and the cut-off value was 0.835, with 80.00% sensitivity and 88.89% specificity.</p><p><strong>Conclusion: </strong>miR-124a expression is downregulated in the plasma, PBMCs, and synovial fluid of RA patients and has a high diagnostic value for RA.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10407829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9962987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reduction of Missed Diagnosis of G6PD Deficiency in Heterozygous Females by G6PD/6PGD Ratio Assay Combined with Amplification Refractory Mutation System PCR. 通过 G6PD/6PGD 比率测定结合扩增难治性突变系统 PCR,减少杂合子女性 G6PD 缺乏症的漏诊。
IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-01 Epub Date: 2022-10-31 DOI: 10.1159/000527806
Shiguo Chen, Jian Gao, Qunyan Wu, Xi Li, Sheng Lin, Jindi Su, Kaifeng Zheng, Zhaopeng Guo, Jilong Yao, Shan Duan

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that results in impaired enzyme activity. The G6PD/6PGD ratio assay was routinely used for G6PD deficiency screening in China, but there is an apparent defect of missed diagnosis in heterozygous females. The study aims to explore the means to improve its accuracy.

Methods: A total of 4,161 Chinese females of childbearing age were collected in this retrospective study. All samples were first subjected to G6PD/6PGD ratio assay and then screened by amplification refractory mutation system PCR (ARMS-PCR) for six hotspot mutants in Chinese population (c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.392G>T, and c.871G>A). For the samples with G6PD/6PGD ratio<1.0 and no mutations were found by ARMS-PCR, next-generation sequencing (NGS) was performed. Sanger sequencing was finally used to verify all the variants.

Results: The prevalence of G6PD deficiency in Shenzhen females of childbearing age was 7.31%. The proportion of the six hotspot mutations accounted for 98.03% of all 304 G6PD variants carriers. Taking the ARMS-PCR/NGS results as a reference, the missed diagnosis rate of the G6PD/6PGD ratio assay was 33.88%. Using ARMS-PCR to retest the samples with a G6PD/6PGD ratio between 1.00 and ∼1.10 or 1.00 and ∼1.15 could reduce the missed diagnosis rate from the original 33.88% to 18.09% or 12.05% separately.

Conclusion: ARMS-PCR is an appropriate supplementary method for discovering most carriers missed by the G6PD/6PGD ratio assay.

目的:葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症是一种导致酶活性受损的 X 连锁遗传疾病。在中国,G6PD/6PGD比值测定已被常规用于G6PD缺乏症的筛查,但在杂合子女性中存在明显的漏诊缺陷。本研究旨在探索提高其准确性的方法:这项回顾性研究共收集了 4,161 名中国育龄女性的样本。所有样本首先进行G6PD/6PGD比值测定,然后通过扩增难治性突变系统PCR(ARMS-PCR)筛查中国人群中的6个热点突变体(c.1376G>T、c.1388G>A、c.95A>G、c.1024C>T、c.392G>T和c.871G>A)。对于具有 G6PD/6PGD 比率的样本结果如下:深圳育龄女性的 G6PD 缺乏症患病率为 7.31%。在304名G6PD变异携带者中,6个热点变异所占比例为98.03%。以 ARMS-PCR/NGS 结果为参考,G6PD/6PGD 比值检测的漏诊率为 33.88%。使用 ARMS-PCR 对 G6PD/6PGD 比值介于 1.00 与 1.10 之间或 1.00 与 1.15 之间的样本进行复检,可将漏诊率从原来的 33.88% 分别降至 18.09% 或 12.05%:结论:ARMS-PCR是发现G6PD/6PGD比值检测漏诊的大多数携带者的适当辅助方法。
{"title":"Reduction of Missed Diagnosis of G6PD Deficiency in Heterozygous Females by G6PD/6PGD Ratio Assay Combined with Amplification Refractory Mutation System PCR.","authors":"Shiguo Chen, Jian Gao, Qunyan Wu, Xi Li, Sheng Lin, Jindi Su, Kaifeng Zheng, Zhaopeng Guo, Jilong Yao, Shan Duan","doi":"10.1159/000527806","DOIUrl":"10.1159/000527806","url":null,"abstract":"<p><strong>Objective: </strong>Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that results in impaired enzyme activity. The G6PD/6PGD ratio assay was routinely used for G6PD deficiency screening in China, but there is an apparent defect of missed diagnosis in heterozygous females. The study aims to explore the means to improve its accuracy.</p><p><strong>Methods: </strong>A total of 4,161 Chinese females of childbearing age were collected in this retrospective study. All samples were first subjected to G6PD/6PGD ratio assay and then screened by amplification refractory mutation system PCR (ARMS-PCR) for six hotspot mutants in Chinese population (c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.392G>T, and c.871G>A). For the samples with G6PD/6PGD ratio<1.0 and no mutations were found by ARMS-PCR, next-generation sequencing (NGS) was performed. Sanger sequencing was finally used to verify all the variants.</p><p><strong>Results: </strong>The prevalence of G6PD deficiency in Shenzhen females of childbearing age was 7.31%. The proportion of the six hotspot mutations accounted for 98.03% of all 304 G6PD variants carriers. Taking the ARMS-PCR/NGS results as a reference, the missed diagnosis rate of the G6PD/6PGD ratio assay was 33.88%. Using ARMS-PCR to retest the samples with a G6PD/6PGD ratio between 1.00 and ∼1.10 or 1.00 and ∼1.15 could reduce the missed diagnosis rate from the original 33.88% to 18.09% or 12.05% separately.</p><p><strong>Conclusion: </strong>ARMS-PCR is an appropriate supplementary method for discovering most carriers missed by the G6PD/6PGD ratio assay.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9254952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Common Variant of ARRB2 Promoter Region Associated with the Prognosis of Heart Failure. ARRB2启动子区常见变异与心力衰竭预后的关系。
IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-01 Epub Date: 2023-04-26 DOI: 10.1159/000530827
Hongqiang Ren, Yijun Liu, Zhen Tan, Guiquan Luo, Mei Zhang, Shuang Li, Tingwei Tang, Li Zhao

Introduction: The role of ARRB2 in cardiovascular disease has recently gained increasing attention. However, the association between ARRB2 polymorphisms and heart failure (HF) has not yet been investigated.

Methods: A total of 2,386 hospitalized patients with chronic HF were enrolled as the first cohort and followed up for a mean period of 20.2 months. Meanwhile, ethnically and geographically matched 3,000 individuals without evidence of HF were included as healthy controls. We genotyped the common variant in ARRB2 gene to identify the association between variant and HF. A replicated independent cohort enrolling 837 patients with chronic HF was applied to validate the observed association. A series of function analyses were conducted to illuminate the underlying mechanism.

Results: We identified a common variant rs75428611 associated with the prognosis of HF in two-stage population: adjusted p = 0.001, hazard ratio (HR) = 1.31 (1.11-1.54) in additive model and adjusted p = 0.001, HR = 1.39 (1.14-1.69) in dominant model in first-stage population; adjusted p = 0.04, HR = 1.41 (1.02-1.95) in additive model and adjusted p = 0.03, HR = 1.51 (1.03-2.20) in dominant model in replicated stage. However, rs75428611 did not significantly associate with the risk of HF. Functional analysis indicated that rs75428611-G allele increased the promoter activity and the mRNA expression level of ARRB2 by facilitating transcription factor SRF binding but not the A allele.

Conclusions: Our findings demonstrated that rs75428611 in promoter of ARRB2 was associated with the risk of HF mortality. It is a promising potential treatment target for HF.

引言:ARRB2在心血管疾病中的作用最近越来越受到关注。然而,ARRB2多态性与心力衰竭(HF)之间的关系尚未得到研究。方法:共有2386名慢性心衰住院患者被纳入第一队列,平均随访20.2个月。同时,在种族和地理上匹配的3000名没有HF证据的人被纳入健康对照。我们对ARRB2基因的常见变体进行了基因分型,以确定变体与HF之间的相关性。采用一个复制的独立队列,纳入837名慢性HF患者,以验证观察到的相关性。进行了一系列功能分析,以阐明潜在的机制。结果:在两阶段人群中,我们发现了一个与HF预后相关的常见变异rs75428611:在加性模型中,调整后的p=0.001,危险比(HR)=1.31(1.11-1.54),在第一阶段人群的显性模型中,校正后的p=0.001,HR=1.39(1.14-1.69);在复制期,加性模型中调整p=0.04,HR=1.41(1.02-1.95),显性模型中调整p=0.03,HR=1.51(1.03-2.20)。功能分析表明,rs75428611-G等位基因通过促进转录因子SRF结合而不是A等位基因,从而提高ARRB2的启动子活性和mRNA表达水平。结论:我们的研究结果表明ARRB2启动子中的rs75428611与HF死亡率相关。它是一个很有前途的治疗HF的潜在靶点。
{"title":"A Common Variant of ARRB2 Promoter Region Associated with the Prognosis of Heart Failure.","authors":"Hongqiang Ren, Yijun Liu, Zhen Tan, Guiquan Luo, Mei Zhang, Shuang Li, Tingwei Tang, Li Zhao","doi":"10.1159/000530827","DOIUrl":"10.1159/000530827","url":null,"abstract":"<p><strong>Introduction: </strong>The role of ARRB2 in cardiovascular disease has recently gained increasing attention. However, the association between ARRB2 polymorphisms and heart failure (HF) has not yet been investigated.</p><p><strong>Methods: </strong>A total of 2,386 hospitalized patients with chronic HF were enrolled as the first cohort and followed up for a mean period of 20.2 months. Meanwhile, ethnically and geographically matched 3,000 individuals without evidence of HF were included as healthy controls. We genotyped the common variant in ARRB2 gene to identify the association between variant and HF. A replicated independent cohort enrolling 837 patients with chronic HF was applied to validate the observed association. A series of function analyses were conducted to illuminate the underlying mechanism.</p><p><strong>Results: </strong>We identified a common variant rs75428611 associated with the prognosis of HF in two-stage population: adjusted p = 0.001, hazard ratio (HR) = 1.31 (1.11-1.54) in additive model and adjusted p = 0.001, HR = 1.39 (1.14-1.69) in dominant model in first-stage population; adjusted p = 0.04, HR = 1.41 (1.02-1.95) in additive model and adjusted p = 0.03, HR = 1.51 (1.03-2.20) in dominant model in replicated stage. However, rs75428611 did not significantly associate with the risk of HF. Functional analysis indicated that rs75428611-G allele increased the promoter activity and the mRNA expression level of ARRB2 by facilitating transcription factor SRF binding but not the A allele.</p><p><strong>Conclusions: </strong>Our findings demonstrated that rs75428611 in promoter of ARRB2 was associated with the risk of HF mortality. It is a promising potential treatment target for HF.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9351239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Novel PMVK Variant Associated with Familial Porokeratosis. 一种与家族性角化病有关的新型 PMVK 变体
IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-01 Epub Date: 2023-06-14 DOI: 10.1159/000531120
Wenjing Zhang, Xinmiao Nie, Lei Shi, Fengmin Shao, Lihua Cao

Background: Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including phosphomevalonate kinase (PMVK) may alter this pathway, ultimately leading to porokeratosis.

Objectives: The aim of the study was to identify the causative gene variant of porokeratosis in a Chinese family and investigate its population frequency and pathogenicity.

Method: In this study, Sanger sequencing was used to identify the gene variant causative of porokeratosis; its population frequency was investigated by polymerase chain reaction-restriction fragment length polymorphism in 4 patients and three normal individuals as well as in 100 normal unrelated controls; finally, the pathogenicity of the mutation and the associated structural changes were predicted.

Results: We identified a novel heterozygous missense variant, c.207G>T (p. Lys69Asn) in the PMVK gene. This variant was found in all patients but not in the normal individuals in this family or in the 100 controls. In silico analysis indicated that the variant was pathogenic; p.Lys69Asn changed the length of the α-helix and the hydrogen bond pattern compared with the wild-type protein.

Conclusions: The novel variant c.207G>T (p. Lys69Asn) in the PMVK gene was the causative variant in this porokeratosis family. This finding provides further evidence for the genetic basis of this disease.

背景:角化病是一种罕见的慢性进行性角化不全皮肤病,可能与甲羟戊酸途径有关。包括磷酸甲羟戊酸激酶(PMVK)在内的四种酶的变异可能会改变这一途径,最终导致角化病:本研究的目的是在一个中国家族中确定 porokeratosis 的致病基因变异,并调查其人群频率和致病性:方法:本研究采用桑格测序法鉴定了导致角化病的基因变异,并通过聚合酶链式反应-限制性片段长度多态性研究了该变异在4名患者、3名正常人和100名正常非亲属对照中的人群频率,最后预测了该变异的致病性和相关结构变化:结果:我们在 PMVK 基因中发现了一个新的杂合错义变异,c.207G>T (p. Lys69Asn)。该变异在所有患者中均有发现,但在该家族的正常人和 100 名对照者中却没有发现。硅学分析表明,该变体具有致病性;与野生型蛋白相比,p.Lys69Asn 改变了 α-螺旋的长度和氢键模式:结论:PMVK基因中的新型变异体c.207G>T(p. Lys69Asn)是这个角化病家族的致病变异体。这一发现为该疾病的遗传基础提供了进一步的证据。
{"title":"A Novel PMVK Variant Associated with Familial Porokeratosis.","authors":"Wenjing Zhang, Xinmiao Nie, Lei Shi, Fengmin Shao, Lihua Cao","doi":"10.1159/000531120","DOIUrl":"10.1159/000531120","url":null,"abstract":"<p><strong>Background: </strong>Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including phosphomevalonate kinase (PMVK) may alter this pathway, ultimately leading to porokeratosis.</p><p><strong>Objectives: </strong>The aim of the study was to identify the causative gene variant of porokeratosis in a Chinese family and investigate its population frequency and pathogenicity.</p><p><strong>Method: </strong>In this study, Sanger sequencing was used to identify the gene variant causative of porokeratosis; its population frequency was investigated by polymerase chain reaction-restriction fragment length polymorphism in 4 patients and three normal individuals as well as in 100 normal unrelated controls; finally, the pathogenicity of the mutation and the associated structural changes were predicted.</p><p><strong>Results: </strong>We identified a novel heterozygous missense variant, c.207G&gt;T (p. Lys69Asn) in the PMVK gene. This variant was found in all patients but not in the normal individuals in this family or in the 100 controls. In silico analysis indicated that the variant was pathogenic; p.Lys69Asn changed the length of the α-helix and the hydrogen bond pattern compared with the wild-type protein.</p><p><strong>Conclusions: </strong>The novel variant c.207G&gt;T (p. Lys69Asn) in the PMVK gene was the causative variant in this porokeratosis family. This finding provides further evidence for the genetic basis of this disease.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9632284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Comprehensive Study of Disease-Causing Variants in PAH, QDPR, PTS, and PCD Genes in Iranian Patients with Hyperphenylalaninemia: A Systematic Review. 伊朗高苯丙氨酸血症患者中 PAH、QDPR、PTS 和 PCD 基因致病变异的综合研究:系统回顾
IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-01 Epub Date: 2023-01-16 DOI: 10.1159/000529037
Mahmoud Ghanei, Seyedeh Helia Sadat Fatemi, Tayebeh Hamzehlouei

Background: Hyperphenylalaninemia (HPA) is an autosomal recessive disorder that results from a deficiency in the phenylalanine hydroxylase enzyme (PAH) or from a flaw in the genes that are responsible for the biosynthesis or regeneration of the cofactor tetrahydrobiopterin (BH4), including GCH1, SR, QDPR, PTS, and PCD. Identification of disease-causing variants in these genes can help physicians and clinical geneticists in differential diagnosis, appropriate prescription drugs, and saving time and cost. This study attempted to identify these genes' most prevalent disease-causing variants in Iranian HPA patients.

Summary: This study was performed under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Before it started, the flow work and inclusion/exclusion criteria were published as a protocol in PROSPERO (CRD42021273705). We conducted a comprehensive search on December 10, 2022, on international online databases, including Web of Science, Scopus, EMBASE, Science Direct, PubMed/Medline, Google Scholar, SID, ISC, and Magiran search engine, to find pertinent publications. Some studies were chosen based on inclusion and exclusion criteria. Altogether, 1,243 Iranian patients from 13 articles were considered. In total, we identified 129 distinct disease-causing variants in PAH (20 novel variants), 29 in QDPR (17 novel variants), 15 in PTS (seven novel variants), and one novel variant in PCD. Twenty disease-causing variants for PAH, 18 for QDPR, and 8 for PTS are included in the genes' proposed genetic diagnostic panels. These panels include more than 75% of the documented disease-causing variants in the Iranian population.

Key messages: The findings of this research illustrated the spectrum of disease-causing variants in the PAH, QDPR, PTS, and PCD genes identified in Iranian HPA patients. Common disease-causing variants of these genes may be chosen as a preliminary diagnostic panel for early diagnosis and lowering therapy costs.

背景:高苯丙氨酸血症(HPA)是一种常染色体隐性遗传疾病,由苯丙氨酸羟化酶(PAH)缺乏或负责辅因子四氢生物蝶呤(BH4)的生物合成或再生的基因缺陷引起,包括 GCH1、SR、QDPR、PTS 和 PCD。鉴定这些基因中的致病变异体有助于医生和临床遗传学家进行鉴别诊断、对症下药并节省时间和成本。本研究试图确定这些基因在伊朗 HPA 患者中最普遍的致病变异。摘要:本研究根据系统综述和荟萃分析首选报告项目(PRISMA)指南进行。在研究开始之前,研究流程和纳入/排除标准已作为协议发布在 PROSPERO (CRD42021273705)上。我们于 2022 年 12 月 10 日在国际在线数据库(包括 Web of Science、Scopus、EMBASE、Science Direct、PubMed/Medline、Google Scholar、SID、ISC 和 Magiran 搜索引擎)中进行了全面搜索,以找到相关出版物。根据纳入和排除标准选择了一些研究。共考虑了 13 篇文章中的 1,243 名伊朗患者。我们总共发现了 129 个不同的 PAH 致病变异体(20 个新型变异体)、29 个 QDPR 致病变异体(17 个新型变异体)、15 个 PTS 致病变异体(7 个新型变异体)和 1 个 PCD 致病变异体。PAH 的 20 个致病变异体、QDPR 的 18 个致病变异体和 PTS 的 8 个致病变异体已被纳入基因的拟议基因诊断面板中。这些基因组包括了伊朗人口中超过 75% 已记录的致病变体:本研究结果说明了在伊朗 HPA 患者中发现的 PAH、QDPR、PTS 和 PCD 基因致病变异的范围。可选择这些基因中的常见致病变异作为初步诊断面板,以进行早期诊断并降低治疗成本。
{"title":"A Comprehensive Study of Disease-Causing Variants in PAH, QDPR, PTS, and PCD Genes in Iranian Patients with Hyperphenylalaninemia: A Systematic Review.","authors":"Mahmoud Ghanei, Seyedeh Helia Sadat Fatemi, Tayebeh Hamzehlouei","doi":"10.1159/000529037","DOIUrl":"10.1159/000529037","url":null,"abstract":"<p><strong>Background: </strong>Hyperphenylalaninemia (HPA) is an autosomal recessive disorder that results from a deficiency in the phenylalanine hydroxylase enzyme (PAH) or from a flaw in the genes that are responsible for the biosynthesis or regeneration of the cofactor tetrahydrobiopterin (BH4), including GCH1, SR, QDPR, PTS, and PCD. Identification of disease-causing variants in these genes can help physicians and clinical geneticists in differential diagnosis, appropriate prescription drugs, and saving time and cost. This study attempted to identify these genes' most prevalent disease-causing variants in Iranian HPA patients.</p><p><strong>Summary: </strong>This study was performed under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Before it started, the flow work and inclusion/exclusion criteria were published as a protocol in PROSPERO (CRD42021273705). We conducted a comprehensive search on December 10, 2022, on international online databases, including Web of Science, Scopus, EMBASE, Science Direct, PubMed/Medline, Google Scholar, SID, ISC, and Magiran search engine, to find pertinent publications. Some studies were chosen based on inclusion and exclusion criteria. Altogether, 1,243 Iranian patients from 13 articles were considered. In total, we identified 129 distinct disease-causing variants in PAH (20 novel variants), 29 in QDPR (17 novel variants), 15 in PTS (seven novel variants), and one novel variant in PCD. Twenty disease-causing variants for PAH, 18 for QDPR, and 8 for PTS are included in the genes' proposed genetic diagnostic panels. These panels include more than 75% of the documented disease-causing variants in the Iranian population.</p><p><strong>Key messages: </strong>The findings of this research illustrated the spectrum of disease-causing variants in the PAH, QDPR, PTS, and PCD genes identified in Iranian HPA patients. Common disease-causing variants of these genes may be chosen as a preliminary diagnostic panel for early diagnosis and lowering therapy costs.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10750328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10527867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Novel c.3636-4 A>G Mutation in the CCDC88C Plays a Causative Role in Familial Spinocerebellar Ataxia. CCDC88C中一个新的c.3636-4 A>G突变在家族性脊髓小脑共济失调中起致病作用。
IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-01 Epub Date: 2023-10-27 DOI: 10.1159/000534692
Senmao Chai, Deyang Liu, Yajing Liu, Ming Sang

Introduction: Spinocerebellar ataxia (SCA) is an autosomal dominant genetic disease characterized by cerebellar neurological deficits. Specifically, its primary clinical manifestation is ataxia accompanied by peripheral nerve damage. A total of 48 causative genes of SCA have been identified. This study aimed to identify causative genes of autosomal dominant SCA in a four-generation Chinese kindred comprising eight affected individuals.

Methods: Genomic DNA samples were extracted from the pedigree members, and genomic whole-exome sequencing was performed, followed by bidirectional Sanger sequencing, and minigene assays to identify mutation sites.

Results: A novel pathogenic heterozygous mutation in the splice region of the coiled-coil domain containing the 88C (CCDC88C) gene (NM_001080414:c.3636-4 A>G) was identified in four affected members. The minigene assay results indicated that this mutation leads to the insertion of CAG bases (c.3636-1_3636-3 insCAG).

Conclusion: CCDC88C gene mutation leads to SCA40 (OMIM:616053), which is a rare subtype of SCA without symptoms during childhood. Our findings further demonstrated the role of the CCDC88C gene in SCA and indicated that the c.3636-4 A>G (NM_001080414) variant of CCDC88C is causative for a later-onset phenotype of SCA40. Our findings enrich the mutation spectrum of CCDC88C gene and provide a theoretical basis for the genetic counseling of SCA40.

简介:脊髓角性共济失调(SCA)是一种以小脑神经功能缺损为特征的常染色体显性遗传疾病。具体而言,其主要临床表现为共济失调伴周围神经损伤。共鉴定出48个SCA致病基因。本研究旨在鉴定一个由八个患病个体组成的四代中国家族中常染色体显性SCA的致病基因。方法:从家系成员中提取基因组DNA样本,进行基因组全外显子组测序(WES),然后进行双向Sanger测序和小基因分析以鉴定突变位点。结果:在四个受影响的成员中,在含有88C(CCDC88C)基因的卷曲螺旋结构域的剪接区发现了一个新的致病性杂合突变(NM_001080414:c.3636-4 A>G)。CCDC88C基因突变导致SCA40(OMIM:616053),这是一种罕见的儿童期无症状SCA亚型。我们的研究结果进一步证明了CCDC88C基因在SCA中的作用,并表明CCDC88C的c.3636-4 A>G(NM_001080414)变体是SCA40晚发表型的原因。我们的发现丰富了CCDC88C基因的突变谱,为SCA40的遗传咨询提供了理论依据。
{"title":"A Novel c.3636-4 A&gt;G Mutation in the CCDC88C Plays a Causative Role in Familial Spinocerebellar Ataxia.","authors":"Senmao Chai, Deyang Liu, Yajing Liu, Ming Sang","doi":"10.1159/000534692","DOIUrl":"10.1159/000534692","url":null,"abstract":"<p><strong>Introduction: </strong>Spinocerebellar ataxia (SCA) is an autosomal dominant genetic disease characterized by cerebellar neurological deficits. Specifically, its primary clinical manifestation is ataxia accompanied by peripheral nerve damage. A total of 48 causative genes of SCA have been identified. This study aimed to identify causative genes of autosomal dominant SCA in a four-generation Chinese kindred comprising eight affected individuals.</p><p><strong>Methods: </strong>Genomic DNA samples were extracted from the pedigree members, and genomic whole-exome sequencing was performed, followed by bidirectional Sanger sequencing, and minigene assays to identify mutation sites.</p><p><strong>Results: </strong>A novel pathogenic heterozygous mutation in the splice region of the coiled-coil domain containing the 88C (CCDC88C) gene (NM_001080414:c.3636-4 A&gt;G) was identified in four affected members. The minigene assay results indicated that this mutation leads to the insertion of CAG bases (c.3636-1_3636-3 insCAG).</p><p><strong>Conclusion: </strong>CCDC88C gene mutation leads to SCA40 (OMIM:616053), which is a rare subtype of SCA without symptoms during childhood. Our findings further demonstrated the role of the CCDC88C gene in SCA and indicated that the c.3636-4 A&gt;G (NM_001080414) variant of CCDC88C is causative for a later-onset phenotype of SCA40. Our findings enrich the mutation spectrum of CCDC88C gene and provide a theoretical basis for the genetic counseling of SCA40.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Violation of the constant genetic effect assumption can result in biased estimates for non-linear Mendelian randomization 违反恒定遗传效应假设可能导致对非线性孟德尔随机化的有偏估计
IF 1.8 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-31 DOI: 10.1101/2022.10.26.22280570
S. Burgess
Non-linear Mendelian randomization is an extension of conventional Mendelian randomization that performs separate instrumental variable analyses in strata of the study population with different average levels of the exposure. The approach estimates a localized average causal effect function, representing the average causal effect of the exposure on the outcome at different levels of the exposure. The commonly-used residual method for dividing the population into strata works under the assumption that the effect of the genetic instrument on the exposure is linear and constant in the study population. However, this assumption may not hold in practice. We use the recently developed doubly-ranked method to re-analyse various datasets previously analysed using the residual method. In particular, we consider a genetic score for 25-hydroxyvitamin D [25(OH)D] used in a recent non-linear Mendelian randomization analysis to assess the potential effect of vitamin D supplementation on all-cause mortality. We show that the effect of the genetic score on 25(OH)D concentrations varies strongly, with a five-fold difference in the estimated genetic association with the exposure in the lowest and highest decile groups. Evidence for a protective causal effect of vitamin D supplementation on all-cause mortality in low vitamin D individuals is evident for the residual method, but not for the doubly-ranked method. We show that the constant genetic effect assumption is more reasonable for some exposures, and less reasonable for others. If the doubly-ranked method indicates that this assumption is violated, then estimates from both the residual and doubly-ranked methods can be biased, although bias was smaller on average in the doubly-ranked method. Analysts should compare results from both methods, as well as considering transforming the exposure to reduce heterogeneity in the genetic effect on the exposure.
非线性孟德尔随机化是传统孟德尔随机化的扩展,在具有不同平均暴露水平的研究人群的阶层中进行单独的工具变量分析。该方法估计了局部平均因果效应函数,表示不同暴露水平下暴露对结果的平均因果效应。将人群划分为阶层的常用残差方法是在假设遗传工具对研究人群暴露的影响是线性和恒定的情况下工作的。然而,这一假设在实践中可能并不成立。我们使用最近开发的双重排序方法来重新分析以前使用残差方法分析的各种数据集。特别是,我们考虑了最近一项非线性孟德尔随机化分析中使用的25-羟基维生素D[25(OH)D]的遗传评分,以评估补充维生素D对全因死亡率的潜在影响。我们发现,遗传评分对25(OH)D浓度的影响变化很大,在最低和最高十分位数组中,估计的遗传关联与暴露量相差五倍。维生素D补充对低维生素D人群全因死亡率的保护性因果效应的证据在残差法中是明显的,但在双重排序法中则不然。我们表明,恒定遗传效应假设对某些暴露更合理,而对其他暴露则不太合理。如果双重排序方法表明违反了这一假设,那么残差和双重排序方法的估计都可能有偏差,尽管双重排序方法中的偏差平均较小。分析人员应比较两种方法的结果,并考虑改变暴露,以减少遗传效应对暴露的异质性。
{"title":"Violation of the constant genetic effect assumption can result in biased estimates for non-linear Mendelian randomization","authors":"S. Burgess","doi":"10.1101/2022.10.26.22280570","DOIUrl":"https://doi.org/10.1101/2022.10.26.22280570","url":null,"abstract":"Non-linear Mendelian randomization is an extension of conventional Mendelian randomization that performs separate instrumental variable analyses in strata of the study population with different average levels of the exposure. The approach estimates a localized average causal effect function, representing the average causal effect of the exposure on the outcome at different levels of the exposure. The commonly-used residual method for dividing the population into strata works under the assumption that the effect of the genetic instrument on the exposure is linear and constant in the study population. However, this assumption may not hold in practice. We use the recently developed doubly-ranked method to re-analyse various datasets previously analysed using the residual method. In particular, we consider a genetic score for 25-hydroxyvitamin D [25(OH)D] used in a recent non-linear Mendelian randomization analysis to assess the potential effect of vitamin D supplementation on all-cause mortality. We show that the effect of the genetic score on 25(OH)D concentrations varies strongly, with a five-fold difference in the estimated genetic association with the exposure in the lowest and highest decile groups. Evidence for a protective causal effect of vitamin D supplementation on all-cause mortality in low vitamin D individuals is evident for the residual method, but not for the doubly-ranked method. We show that the constant genetic effect assumption is more reasonable for some exposures, and less reasonable for others. If the doubly-ranked method indicates that this assumption is violated, then estimates from both the residual and doubly-ranked methods can be biased, although bias was smaller on average in the doubly-ranked method. Analysts should compare results from both methods, as well as considering transforming the exposure to reduce heterogeneity in the genetic effect on the exposure.","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41898686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
The prevalence of JAK2 exon12 mutations in Vietnamese patients with JAK2 V617F-negative polycythemia vera: frequent or rare? JAK2 V617F阴性多发性红细胞症越南患者中JAK2外显子12突变的发生率:常见还是罕见?
IF 1.8 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-08-03 DOI: 10.1159/000526201
Ngoc T Nguyen, Linh T Nguyen, Xuan T Nguyen

Purpose Polycythemia vera is a hematological malignancy characterized by the overproduction of red blood cells in the bone marrow. Pathogenesis of Polycythemia vera was thought to be caused by genetic mutations of the Janus kinase 2 (JAK2) gene, especially the JAK2 V617F and exon 12 mutations since those mutations were found frequently in the patients. The prevalence of JAK2 exon 12 mutations among Polycythemia Vera patients in Vietnam has not been studied yet. Objectives The overall study objective is to investigate the frequency of JAK2 exon 12 mutations among V617F-negative Polycythemia Vera patients in Vietnam. Methods In this study, the occurrence of these mutations was investigated in a clinical population of 76 Vietnamese Polycythemia Vera patients by PCR-RFLP and Sanger sequencing. Results The result showed that 53 of the patients were V617F-positive, and in 23 V617F-negative patients, only four individuals carried two JAK2 exon 12 mutations. Analysis by different in-silico tools predicted that all the two exon 12 mutations detected in this study (JAK2 c.1592A>G; p.H531R and c.1616A>G p.K539R) were benign. Conclusion These results suggested that the causative mutations in this V617F-negative subgroup might locate in another genetic region, and mutations in exon 12 might not be as common among the V617F-negative Polycythemia Vera patients as thought.

目的 多发性红细胞增多症是一种以骨髓中红细胞生成过多为特征的血液系统恶性肿瘤。多发性红细胞症的发病机制被认为是由 Janus 激酶 2(JAK2)基因突变引起的,尤其是 JAK2 V617F 和第 12 号外显子突变,因为这些突变在患者中经常出现。越南的多发性红细胞增多症患者中 JAK2 第 12 号外显子突变的发生率尚未得到研究。目的 研究的总体目标是调查越南 V617F 阴性多发性红细胞增多症患者中 JAK2 第 12 号外显子突变的发生率。方法 本研究通过 PCR-RFLP 和 Sanger 测序,对 76 例越南多发性红细胞增多症患者的临床人群中这些突变的发生率进行了调查。结果显示,53 例患者为 V617F 阳性,23 例 V617F 阴性患者中仅有 4 例携带两个 JAK2 第 12 外显子突变。通过不同的体内工具分析预测,本研究中检测到的两个第12外显子突变(JAK2 c.1592A>G; p.H531R和c.1616A>G p.K539R)均为良性突变。结论 这些结果表明,V617F 阴性亚组中的致病突变可能位于另一个基因区域,V617F 阴性多发性红细胞症患者中第 12 外显子突变可能并不像想象的那样常见。
{"title":"The prevalence of JAK2 exon12 mutations in Vietnamese patients with JAK2 V617F-negative polycythemia vera: frequent or rare?","authors":"Ngoc T Nguyen, Linh T Nguyen, Xuan T Nguyen","doi":"10.1159/000526201","DOIUrl":"10.1159/000526201","url":null,"abstract":"<p><p>Purpose Polycythemia vera is a hematological malignancy characterized by the overproduction of red blood cells in the bone marrow. Pathogenesis of Polycythemia vera was thought to be caused by genetic mutations of the Janus kinase 2 (JAK2) gene, especially the JAK2 V617F and exon 12 mutations since those mutations were found frequently in the patients. The prevalence of JAK2 exon 12 mutations among Polycythemia Vera patients in Vietnam has not been studied yet. Objectives The overall study objective is to investigate the frequency of JAK2 exon 12 mutations among V617F-negative Polycythemia Vera patients in Vietnam. Methods In this study, the occurrence of these mutations was investigated in a clinical population of 76 Vietnamese Polycythemia Vera patients by PCR-RFLP and Sanger sequencing. Results The result showed that 53 of the patients were V617F-positive, and in 23 V617F-negative patients, only four individuals carried two JAK2 exon 12 mutations. Analysis by different in-silico tools predicted that all the two exon 12 mutations detected in this study (JAK2 c.1592A>G; p.H531R and c.1616A>G p.K539R) were benign. Conclusion These results suggested that the causative mutations in this V617F-negative subgroup might locate in another genetic region, and mutations in exon 12 might not be as common among the V617F-negative Polycythemia Vera patients as thought.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40581049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Human Heredity
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1