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Biomarker testing for lysosomal diseases: A technical standard of the American College of Medical Genetics and Genomics (ACMG). 溶酶体疾病的生物标志物检测:美国医学遗传学和基因组学学院(ACMG)技术标准。
IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-11-04 DOI: 10.1016/j.gim.2024.101242
Ashlee R Stiles, Taraka R Donti, Patricia L Hall, William R Wilcox

Measurement of lysosomal disease (LD) biomarkers can reveal valuable information about disease status. Lyso-globotriaosylceramide (lyso-Gb3), glucosylsphingosine (lyso-Gb1), galactosylsphingosine (psychosine), and glucose tetrasaccharide (Glca1-6Glca1-4Glca1-4Glc, Glc4) are biomarkers associated with Fabry, Gaucher, Krabbe, and Pompe disease, respectively. Clinical biomarker testing is performed to guide patient management, including monitoring disease progression and initiating treatment, and in diagnostic evaluations of either symptomatic patients or asymptomatic individuals with a positive family history or abnormal newborn screen. Biomarker analysis can be performed through independent analysis of a single analyte or as a multiplex assay measuring analytes for more than one disorder utilizing liquid chromatographic separation and tandem mass spectrometric detection. These guidelines were developed to provide technical standards for biomarker analysis, results interpretation, and results reporting, highlighting Fabry, Gaucher, Krabbe, and Pompe diseases as examples.

溶酶体疾病(LD)生物标志物的测定可揭示有关疾病状况的宝贵信息。溶菌体-球藻糖基甘油酰胺(溶-Gb3)、葡糖基鞘氨醇苷(溶-Gb1)、半乳糖基鞘氨醇苷(psychosine)和葡萄糖四糖(Glca1-6Glca1-4Glca1-4Glc,Glc4)分别是与法布里病、戈谢病、克拉贝病和庞贝病相关的生物标记物。临床生物标记物检测用于指导患者管理,包括监测疾病进展和开始治疗,以及对有症状的患者或有阳性家族史或新生儿筛查异常的无症状患者进行诊断评估。生物标记物分析可以通过对单一分析物进行独立分析,也可以通过液相色谱分离和串联质谱检测对一种以上疾病的分析物进行多重检测。制定这些指南的目的是为生物标记物分析、结果解释和结果报告提供技术标准,并以法布里病、戈谢病、克拉贝病和庞贝病为例加以说明。
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引用次数: 0
Response to Horta et al 对 Horta 等人的回应
IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-11-01 DOI: 10.1016/j.gim.2024.101215
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引用次数: 0
Correspondence on “The ClinGen Brain Malformation Variant Curation Expert Panel: Rules for somatic variants in AKT3, MTOR, PIK3CA, and PIK3R2” by Lai et al 关于 "ClinGen 脑畸形变异编辑专家小组:Lai等人撰写的 "AKT3、MTOR、PIK3CA和PIK3R2体细胞变异规则"。
IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-11-01 DOI: 10.1016/j.gim.2024.101214
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引用次数: 0
Primary care provider practices, attitudes, and confidence with hereditary cancer risk assessment and testing: A mixed methods study. 初级保健提供者对遗传性癌症风险评估和检测的做法、态度和信心:混合方法研究。
IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-28 DOI: 10.1016/j.gim.2024.101307
Sarah Conner, Tesla Theoryn, Emerson Dusic, Faith Beers, Sarah Knerr, Barbara Norquist, Brian H Shirts, Deborah Bowen, Elizabeth M Swisher, Catharine Wang

Purpose: This study sought to better understand primary care providers' (PCPs) readiness to conduct population-based risk assessment and offer genetic testing for hereditary cancer.

Methods: Sixty PCPs completed a survey assessing their current practices, attitudes, and confidence with cancer risk assessment and testing. Sixteen participated in follow-up interviews. Descriptive statistics are presented and supported by qualitative data.

Results: Providers preferred direct questioning over standardized screening tools. In interviews, providers said they are not ordering cancer-risk genetic testing even when it might be appropriate. Ninety-eight percent agree testing is important to clinical care, but 73% agree that it could negatively impact patients. Ninety percent were willing to offer targeted testing, but only 68% were willing to offer population-based risk assessment. Confidence performing different behaviors necessary in a cancer risk assessment varied, with only 32% confident responding to questions specifically related to genetic testing.

Conclusion: Providers are willing to offer genetic testing, but unlikely to do so because they lack confidence in genetics-specific skill areas. Unsystematic approaches to family history screening and fears about follow up complexity may exacerbate health disparities. Interventions to increase provider confidence in ascertaining and managing hereditary cancer are needed to achieve widespread adoption of population-based risk assessment and guideline-recommended genetic testing.

目的:本研究旨在更好地了解初级保健提供者(PCPs)在进行基于人群的风险评估和提供遗传性癌症基因检测方面的准备情况:方法:60 名初级保健医生完成了一项调查,评估他们目前的做法、态度以及对癌症风险评估和检测的信心。16 人参加了后续访谈。结果:医疗服务提供者更倾向于采用直接询问的方式进行癌症风险评估和检测:结果:与标准化筛查工具相比,医疗服务提供者更喜欢直接询问。在访谈中,医疗服务提供者表示,即使在可能合适的情况下,他们也不会要求进行癌症风险基因检测。98%的医疗服务提供者认为基因检测对临床治疗很重要,但73%的医疗服务提供者认为基因检测会对患者产生负面影响。90%的人愿意提供有针对性的检测,但只有68%的人愿意提供基于人群的风险评估。对进行癌症风险评估所需的不同行为的信心各不相同,只有 32% 的人有信心回答与基因检测具体相关的问题:结论:医疗服务提供者愿意提供基因检测,但不太可能这样做,因为他们对基因特定技能领域缺乏信心。不系统的家族史筛查方法和对随访复杂性的恐惧可能会加剧健康差异。需要采取干预措施,增强医疗服务提供者对确定和管理遗传性癌症的信心,以实现广泛采用基于人群的风险评估和指南推荐的基因检测。
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引用次数: 0
Trends in and Predictors of Patient Pharmacogenomic Test Uptake in a National Healthcare System. 全国医疗保健系统中患者药物基因组学测试接受趋势和预测因素。
IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-28 DOI: 10.1016/j.gim.2024.101308
Abigail Silva, Deepak Voora, Rebekah Ryanne Wu, Brian Bartle, Catherine Chanfreau-Coffinier, Allison Hung, Corrine I Voils

Purpose: Better understanding patient uptake of pharmacogenomic (PGx) testing may inform its implementation and maximize the benefits that such testing can confer. This study examined patient and provider factors associated with PGx test ordering in a national healthcare system where panel-based testing was implemented as part of routine care.

Methods: We used a retrospective matched cohort design and data from the Veterans Health Administration Corporate Data Warehouse. A conditional logistic model was used to identify factors associated with a PGx order receipt and estimate odds ratios and 95% confidence intervals.

Results: The following patient factors predicted receipt of a PGx test order: younger age, married status, rural residence, non-Hispanic Black or Hispanic race/ethnicity, PGx educational mailer receipt, depression diagnosis, allergy to a drug on the panel, prescriptions for drugs on the panel, and specialty care visits (p<0.05). Additionally, patients whose providers were female, younger, a nurse practitioner/physician assistant or pharmacist, or participated in an educational mailer program were more likely to receive an order (p<0.05).

Conclusion: This study highlights factors that may facilitate or hinder the widespread and equitable implementation of PGx testing in a large national healthcare system. The information is being used to further refine the program.

目的:更好地了解患者对药物基因组学(PGx)检测的接受程度可为其实施提供依据,并最大限度地发挥此类检测所能带来的益处。本研究考察了在一个全国性医疗保健系统中,患者和医疗服务提供者与订购 PGx 检测相关的因素:我们采用了回顾性匹配队列设计,数据来自退伍军人健康管理局企业数据仓库。我们使用条件逻辑模型来确定与收到 PGx 订单相关的因素,并估算出几率比和 95% 的置信区间:结果:以下患者因素可预测是否收到 PGx 检验订单:年龄较小、已婚、农村居民、非西班牙裔黑人或西班牙裔种族/民族、收到 PGx 教育邮件、抑郁症诊断、对面板上的药物过敏、面板上的药物处方以及专科护理就诊(P结论:该研究强调了可能促进 PGx 检验订单的因素,并估算了几率比和 95% 的置信区间:本研究强调了可能促进或阻碍在大型国家医疗保健系统中广泛、公平地实施 PGx 检验的因素。这些信息将用于进一步完善该计划。
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引用次数: 0
Estimation of carrier frequencies of autosomal and X-linked recessive genetic conditions based on gnomAD v4.0 data in different ancestries. 基于 gnomAD v4.0 数据估算不同血统的常染色体和 X 连锁隐性遗传病的携带者频率。
IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-25 DOI: 10.1016/j.gim.2024.101304
Ronja Hotakainen, Timo Järvinen, Kaisa Kettunen, Anna-Kaisa Anttonen, Eveliina Jakkula

Purpose: Monogenic rare diseases contribute significantly to infant deaths and pediatric hospitalizations and cause burden to the patients and their families. The American College of Medical Genetics and Genomics recommended in 2021 that carrier screening of autosomal recessive and X-linked conditions with a carrier frequency of ≥ 1/200 and a severe or moderate phenotype should be offered when planning or during pregnancy. In November 2023 gnomAD v4.0 was released. It contains in total 807,162 individuals, being nearly 5x larger than previous versions, that have been used to estimate gene carrier frequencies (GCF).

Methods: We utilized gnomAD v4.0 (GRCh38) to calculate the GCFs for available genetic ancestry groups for variants having pathogenic or likely pathogenic classification (>80% of submissions) in ClinVar. We calculated GCF separately for exomes and genomes, and combined data, and at-risk couple frequencies (ACF) per genetic ancestry group RESULTS: In total, 324 genes had a GCF ≥ 1/200 in at least one ancestry subgroup. The number of genes with GCF ≥ 1/200 varied greatly between subgroups. ACFs were more similar, Ashkenazi Jewish having the highest ACF of 6.11%.

Conclusion: Improved understanding of carrier risks and updated carrier screening content would allow patients to make more informed reproductive decisions.

目的:单基因罕见病是造成婴儿死亡和儿科住院的重要原因,并给患者及其家庭带来负担。美国医学遗传学和基因组学学院于 2021 年建议,在计划怀孕或怀孕期间,应对携带者频率≥ 1/200 且表型为重度或中度的常染色体隐性遗传病和 X 连锁遗传病进行携带者筛查。2023 年 11 月,gnomAD v4.0 版本发布。它总共包含 807 162 个个体,比以前的版本大近 5 倍,已被用于估算基因携带者频率(GCF):我们利用 gnomAD v4.0 (GRCh38)计算了 ClinVar 中具有致病性或可能致病性分类(>80% 的提交)的变异的可用遗传祖先群体的 GCF。我们分别计算了外显子组和基因组的 GCF 以及合并数据,并计算了每个基因祖先组的高危夫妇频率(ACF) 结果:在至少一个基因祖先亚组中,共有 324 个基因的 GCF ≥ 1/200。不同亚群中 GCF ≥ 1/200 的基因数量差异很大。ACF较为相似,阿什肯纳兹犹太人的ACF最高,为6.11%:结论:提高对携带者风险的认识和更新携带者筛查内容可使患者做出更明智的生育决定。
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引用次数: 0
The Clinician-reported Genetic testing Utility InDEx (C-GUIDE) for Prenatal Care: Initial evidence of content and construct validity. 用于产前护理的临床医师报告基因检测效用 InDEx (C-GUIDE):内容和结构有效性的初步证据。
IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-24 DOI: 10.1016/j.gim.2024.101306
Robin Z Hayeems, Stephanie Luca, Bowen Xiao, Christie Boswell-Patterson, Carolina Lavin Venegas, Clarissa R Abi Semaan, Tessa Kolar, Diane Myles-Reid, Lauren Chad, David Dyment, Kym M Boycott, Joanna Lazier, Wendy J Ungar, Christine M Armour

Objective: To develop and assess the face and construct validity of the Clinician-reported Genetic testing Utility InDEX (C-GUIDETM) for genetic testing in prenatal care.

Methods: Following a literature review and consultation with clinical experts, a preliminary draft of C-GUIDE Prenatal was developed. Its face and content validity were then assessed by 19 prenatal genetics' providers using interviews and surveys. Feedback informed further revisions. To test construct validity, four geneticist raters completed C-GUIDE on a retrospective sample of cases that received prenatal genetic testing and completed a concurrent global assessment of utility of these cases using an anchor item. A generalized estimating equations model was used to adjust for rater correlation and measure the association between C-GUIDE scores, global item scores, and potential clinical variables.

Results: To develop C-GUIDE Prenatal, 7 items were removed, 10 items were modified, and 4 items were added. For 101 cases rated for validation, on average, a 1-point increase in the global item score was associated with an increase of 1.1 in the C-GUIDE score (p=0.04). Compared to uninformative results, informative positive and informative negative results were associated with a mean increase of 10.7 (SE=1.05) (p<0.001) and 5.6 (SE=1.85) (p<0.001), respectively. As indications for testing, known/familial variants were associated with a mean increase in the C-GUIDE score of 4.7 (SE=2.21) (p < 0.001) compared to ultrasound findings. C-GUIDE scores increased by a mean of 3.0 (SE=0.23) among cases for whom pregnancies were ongoing compared to those for whom they were not (p<0.01).

Conclusions: The significant positive associations between C-GUIDE total and the global item score and between C-GUIDE total, result type, indication for testing, and pregnancy status in the expected directions provide evidence of construct validity.

目的开发并评估临床医师报告的产前基因检测效用 InDEX(C-GUIDETM)的表面效度和结构效度:方法:在进行文献回顾并咨询临床专家后,制定了 C-GUIDE Prenatal 初稿。然后,19 名产前遗传学服务提供者通过访谈和调查对其表面和内容有效性进行了评估。反馈意见为进一步修订提供了依据。为了检验构建效度,四位遗传学家对接受产前基因检测的病例进行了回顾性抽样,完成了 C-GUIDE,并同时使用锚点项目对这些病例的效用进行了全面评估。使用广义估计方程模型来调整评分者之间的相关性,并测量 C-GUIDE 评分、全局项目评分和潜在临床变量之间的关联:为了开发 C-GUIDE Prenatal,删除了 7 个项目,修改了 10 个项目,增加了 4 个项目。在 101 个进行验证评分的病例中,总体项目得分每增加 1 分,C-GUIDE 得分平均增加 1.1 分(p=0.04)。与无信息的结果相比,有信息的阳性和阴性结果平均增加 10.7 分(SE=1.05)(p 结论:C-GUIDE总分与总体项目得分之间以及C-GUIDE总分、结果类型、检测指征和妊娠状态之间在预期方向上的显着正相关提供了构建有效性的证据。
{"title":"The Clinician-reported Genetic testing Utility InDEx (C-GUIDE) for Prenatal Care: Initial evidence of content and construct validity.","authors":"Robin Z Hayeems, Stephanie Luca, Bowen Xiao, Christie Boswell-Patterson, Carolina Lavin Venegas, Clarissa R Abi Semaan, Tessa Kolar, Diane Myles-Reid, Lauren Chad, David Dyment, Kym M Boycott, Joanna Lazier, Wendy J Ungar, Christine M Armour","doi":"10.1016/j.gim.2024.101306","DOIUrl":"https://doi.org/10.1016/j.gim.2024.101306","url":null,"abstract":"<p><strong>Objective: </strong>To develop and assess the face and construct validity of the Clinician-reported Genetic testing Utility InDEX (C-GUIDE<sup>TM</sup>) for genetic testing in prenatal care.</p><p><strong>Methods: </strong>Following a literature review and consultation with clinical experts, a preliminary draft of C-GUIDE Prenatal was developed. Its face and content validity were then assessed by 19 prenatal genetics' providers using interviews and surveys. Feedback informed further revisions. To test construct validity, four geneticist raters completed C-GUIDE on a retrospective sample of cases that received prenatal genetic testing and completed a concurrent global assessment of utility of these cases using an anchor item. A generalized estimating equations model was used to adjust for rater correlation and measure the association between C-GUIDE scores, global item scores, and potential clinical variables.</p><p><strong>Results: </strong>To develop C-GUIDE Prenatal, 7 items were removed, 10 items were modified, and 4 items were added. For 101 cases rated for validation, on average, a 1-point increase in the global item score was associated with an increase of 1.1 in the C-GUIDE score (p=0.04). Compared to uninformative results, informative positive and informative negative results were associated with a mean increase of 10.7 (SE=1.05) (p<0.001) and 5.6 (SE=1.85) (p<0.001), respectively. As indications for testing, known/familial variants were associated with a mean increase in the C-GUIDE score of 4.7 (SE=2.21) (p < 0.001) compared to ultrasound findings. C-GUIDE scores increased by a mean of 3.0 (SE=0.23) among cases for whom pregnancies were ongoing compared to those for whom they were not (p<0.01).</p><p><strong>Conclusions: </strong>The significant positive associations between C-GUIDE total and the global item score and between C-GUIDE total, result type, indication for testing, and pregnancy status in the expected directions provide evidence of construct validity.</p>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Classification of Variants of Reduced Penetrance in High Penetrance Cancer Susceptibility Genes: Framework for Genetics Clinicians and Clinical Scientists by CanVIG-UK (Cancer Variant Interpretation Group-UK). 英国癌症变异解释小组(CanVIG-UK)为遗传学临床医生和临床科学家提供的框架:英国癌症变异解释小组(CanVIG-UK)的《遗传学临床医师和临床科学家框架》。
IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-24 DOI: 10.1016/j.gim.2024.101305
Alice Garrett, Sophie Allen, Miranda Durkie, George J Burghel, Rachel Robinson, Alison Callaway, Joanne Field, Bethan Frugtniet, Sheila Palmer-Smith, Jonathan Grant, Judith Pagan, Trudi McDevitt, Charlie F Rowlands, Terri McVeigh, Helen Hanson, Clare Turnbull

Purpose: Current practice is to report and manage likely pathogenic/pathogenic variants in a given cancer susceptibility gene (CSG) as though having equivalent penetrance, despite increasing evidence of inter-variant variability in risk associations. Using existing variant interpretation approaches, largely based on full-penetrance models, variants where reduced penetrance is suspected may be classified inconsistently and/or as variants of uncertain significance (VUS). We aimed to develop a national consensus approach for such variants within the Cancer Variant Interpretation Group UK (CanVIG-UK) multidisciplinary network.

Methods: A series of surveys and live polls were conducted during and between CanVIG-UK monthly meetings on various scenarios potentially indicating reduced penetrance. These informed the iterative development of a framework for the classification of variants of reduced penetrance by the CanVIG-UK Steering and Advisory Group (CStAG) working group.

Results: CanVIG-UK recommendations for amendment of the 2015 ACMG/AMP variant interpretation framework were developed for variants where (A) Active evidence suggests a reduced penetrance effect size (e.g. from case-control or segregation data) (B) Reduced penetrance effect is inferred from weaker/potentially-inconsistent observed data.

Conclusions: CanVIG-UK propose a framework for the classification of variants of reduced penetrance in high-penetrance genes. These principles, whilst developed for CSGs, are potentially applicable to other clinical contexts.

目的:尽管有越来越多的证据表明风险关联中的变异体之间存在差异,但目前的做法是将特定癌症易感基因(CSG)中可能的致病/致病变异体当作具有同等穿透力的变异体进行报告和管理。使用现有的变异解释方法(主要基于全穿透模型),怀疑穿透性降低的变异可能会被不一致地归类和/或归类为意义不确定的变异(VUS)。我们的目标是在英国癌症变异解释小组(CanVIG-UK)多学科网络内为此类变异制定一种全国共识方法:方法:在英国癌症变异解释小组(CanVIG-UK)月度会议期间和会议间隙,针对可能表明穿透性降低的各种情况进行了一系列调查和现场投票。结果:CanVIG-UK 指导和顾问小组 (CStAG) 工作组在反复制定穿透性降低变异体分类框架时参考了这些信息:结果:CanVIG-UK 建议对 2015 年 ACMG/AMP 变异解释框架进行修订,该框架适用于以下变异:(A) 有确凿证据表明渗透率效应大小降低(如病例对照或分离数据);(B) 从较弱/可能不一致的观察数据中推断出渗透率效应降低:CanVIG-UK 提出了一个框架,用于对高渗透性基因中渗透性降低的变异进行分类。这些原则虽然是针对 CSGs 制定的,但有可能适用于其他临床情况。
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引用次数: 0
Impact of early diagnosis, disease variant, and quality of care on the neurocognitive outcome in maple syrup urine disease: a meta-analysis. 早期诊断、疾病变异和护理质量对枫糖尿症神经认知结果的影响:一项荟萃分析。
IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-17 DOI: 10.1016/j.gim.2024.101303
Svenja Scharre, Katharina Mengler, Elena Schnabel, Oya Kuseyri Hübschmann, Ali Tunç Tuncel, Georg Friedrich Hoffmann Gf, Sven F Garbade, Ulrike Mütze, Stefan Kölker

Purpose: Maple syrup urine disease (MSUD) is a rare inherited metabolic disease characterised by recurrent metabolic decompensations, neurocognitive impairment, and limited life expectancy. This meta-analysis aims to evaluate the impact of early diagnosis by newborn screening (NBS) on mortality and neurocognitive outcome in survivors, taking into account the quality of national healthcare systems.

Methods: Systematic literature search was performed according to PRISMA-P. Effects on outcome parameters were analysed using meta-analytical measures and re-analysis of individual participant data.

Results: Thirty-three studies were included, reporting on 1141 individuals with MSUD. Participants with classic MSUD presented a more severe phenotype compared to variant MSUD as demonstrated by higher mortality rate (17.1% versus 0%), and lower median IQ (90 versus 104; P<.001, linear mixed model). NBS was associated with improved cognition (mean IQ: 95 versus 82; P=.014, random effects model), and decreased mortality (3% versus 14.6%; P=.028, Kaplan-Meier estimates) compared to individuals identified after onset of symptoms, in trend even after exclusion of individuals with variant MSUD. Quality of national healthcare systems correlated with survival (P=.025, meta-regression) and permanent neurological symptoms (P=.031, meta-regression).

Conclusion: NBS is a prerequisite to improved outcome in individuals with MSUD; however, health benefit critically depends on the quality of the national healthcare systems.

目的:枫糖尿症(MSUD)是一种罕见的遗传性代谢疾病,其特点是反复出现代谢失代偿、神经认知障碍和预期寿命有限。本荟萃分析旨在评估新生儿筛查(NBS)的早期诊断对幸存者死亡率和神经认知结果的影响,同时考虑到国家医疗保健系统的质量:方法:根据 PRISMA-P 进行系统文献检索。方法:根据 PRISMA-P 进行系统性文献检索,采用荟萃分析方法分析对结果参数的影响,并重新分析个体参与者的数据:结果:共纳入 33 项研究,报告了 1141 名 MSUD 患者。与变异型 MSUD 相比,典型 MSUD 患者的表型更为严重,表现为死亡率更高(17.1% 对 0%),智商中位数更低(90 对 104;PC 结论:NBS 是治疗 MSUD 的先决条件:NBS是改善MSUD患者预后的先决条件;然而,健康效益关键取决于国家医疗保健系统的质量。
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引用次数: 0
The Clinical Genome Resource (ClinGen): Advancing genomic knowledge through global curation. 临床基因组资源(ClinGen):通过全球策划推进基因组知识。
IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-14 DOI: 10.1016/j.gim.2024.101228

The Clinical Genome Resource (ClinGen) is a National Institutes of Health-funded program founded 10 years ago that defines the clinical relevance of genes and variants for medical and research use. ClinGen working groups develop standards for data sharing and curating genomic knowledge. Expert panels, with >2500 active members from 67 countries, curate the validity of monogenic disease relationships, pathogenicity of genetic variation, dosage sensitivity of genes, and actionability of gene-disease interventions using ClinGen standards, infrastructure, and curation interfaces. Results are available on clinicalgenome.org and classified variants are also submitted to ClinVar, a publicly available database hosted by the National Institutes of Health. As of January 2024, over 2700 genes have been curated (2420 gene-disease relationships for validity, 1557 genes for dosage sensitivity, and 447 gene-condition pairs for actionability), and 5161 unique variants have been classified for pathogenicity. New efforts are underway in somatic cancer, complex disease and pharmacogenomics, and a systematic approach to addressing justice, equity, diversity, and inclusion. ClinGen's knowledge can be used to build evidence-based genetic testing panels, interpret copy-number variation, resolve discrepancies in variant classification, guide disclosure of genomic findings to patients, and assess new predictive algorithms. To get involved in ClinGen activities go to https://www.clinicalgenome.org/start.

临床基因组资源(ClinGen)是一项由美国国立卫生研究院资助的计划,成立于 10 年前,旨在定义基因和变异的临床相关性,以供医疗和研究使用。ClinGen 工作组为数据共享和基因组知识整理制定标准。专家小组有来自 67 个国家的超过 2500 名活跃成员,他们利用 ClinGen 标准、基础设施和整理界面,整理单基因疾病关系的有效性、基因变异的致病性、基因的剂量敏感性以及基因疾病干预措施的可操作性。研究结果可在 clinicalgenome.org 网站上查阅,分类变异也可提交至 ClinVar,这是一个由美国国立卫生研究院托管的公开数据库。截至 2024 年 1 月,已对超过 2700 个基因(2420 个基因-疾病关系的有效性、1557 个基因的剂量敏感性和 447 个基因-条件对的可操作性)进行了策划,并对 5161 个独特变异进行了致病性分类。目前正在体细胞癌症、复杂疾病和药物基因组学方面开展新的工作,并采用系统方法来解决公正、公平、多样性和包容性问题。ClinGen 的知识可用于建立循证基因检测面板、解释拷贝数变异、解决变异分类中的差异、指导向患者披露基因组学发现以及评估新的预测算法。要参与 ClinGen 的活动,请访问 https://www.clinicalgenome.org/start。
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引用次数: 0
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