Genetics in Medicine最新文献_第9页

Attitudes, knowledge, and risk perceptions of patients who received elective genomic testing as a clinical service 接受选择性基因组检测作为临床服务的患者的态度、知识和风险认知。

IF 6.6 1区医学

Genetics in Medicine Pub Date : 2024-06-26 DOI: 10.1016/j.gim.2024.101200

{"title":"Attitudes, knowledge, and risk perceptions of patients who received elective genomic testing as a clinical service","authors":"","doi":"10.1016/j.gim.2024.101200","DOIUrl":"10.1016/j.gim.2024.101200","url":null,"abstract":"<div><h3>Purpose</h3><p>Elective genomic testing (EGT) is increasingly available clinically. Limited real-world evidence exists about attitudes and knowledge of EGT recipients.</p></div><div><h3>Methods</h3><p>After web-based education, patients who enrolled in an EGT program at a rural nonprofit health care system completed a survey that assessed attitudes, knowledge, and risk perceptions.</p></div><div><h3>Results</h3><p>From August 2020 to April 2022, 5920 patients completed the survey and received testing. Patients most frequently cited interest in learning their personal disease risks as their primary motivation. Patients most often expected results to guide medication management (74.0%), prevent future disease (70.4%), and provide information about risks to offspring (65.4%). Patients were “very concerned” most frequently about the privacy of genetic information (19.8%) and how well testing predicted disease risks (18.0%). On average, patients answered 6.7 of 11 knowledge items correctly (61.3%). They more often rated their risks for colon and breast cancers as lower rather than higher than the average person but more often rated their risk for a heart attack as higher rather than lower than the average person (all <em>P</em> < .001).</p></div><div><h3>Conclusion</h3><p>Patients pursued EGT because of the utility expectations but often misunderstood the test’s capabilities.</p></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467492","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

Considerations for reporting variants in novel candidate genes identified during clinical genomic testing 报告临床基因组检测中发现的新型候选基因变异的注意事项。

IF 6.6 1区医学

Genetics in Medicine Pub Date : 2024-06-26 DOI: 10.1016/j.gim.2024.101199

{"title":"Considerations for reporting variants in novel candidate genes identified during clinical genomic testing","authors":"","doi":"10.1016/j.gim.2024.101199","DOIUrl":"10.1016/j.gim.2024.101199","url":null,"abstract":"<div><p>Since the first novel gene discovery for a Mendelian condition was made via exome sequencing, the rapid increase in the number of genes known to underlie Mendelian conditions coupled with the adoption of exome (and more recently, genome) sequencing by diagnostic testing labs has changed the landscape of genomic testing for rare diseases. Specifically, many individuals suspected to have a Mendelian condition are now routinely offered clinical ES. This commonly results in a precise genetic diagnosis but frequently overlooks the identification of novel candidate genes. Such candidates are also less likely to be identified in the absence of large-scale gene discovery research programs. Accordingly, clinical laboratories have both the opportunity, and some might argue a responsibility, to contribute to novel gene discovery, which should, in turn, increase the diagnostic yield for many conditions. However, clinical diagnostic laboratories must necessarily balance priorities for throughput, turnaround time, cost efficiency, clinician preferences, and regulatory constraints and often do not have the infrastructure or resources to effectively participate in either clinical translational or basic genome science research efforts. For these and other reasons, many laboratories have historically refrained from broadly sharing potentially pathogenic variants in novel genes via networks such as Matchmaker Exchange, much less reporting such results to ordering providers. Efforts to report such results are further complicated by a lack of guidelines for clinical reporting and interpretation of variants in novel candidate genes. Nevertheless, there are myriad benefits for many stakeholders, including patients/families, clinicians, and researchers, if clinical laboratories systematically and routinely identify, share, and report novel candidate genes. To facilitate this change in practice, we developed criteria for triaging, sharing, and reporting novel candidate genes that are most likely to be promptly validated as underlying a Mendelian condition and translated to use in clinical settings.</p></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467504","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

Parents’ and patients’ perspectives, experiences, and preferences for germline genetic or genomic testing of children with cancer: A systematic review 父母和患者对癌症患儿种系遗传或基因组检测的看法、经验和偏好：系统综述。

IF 6.6 1区医学

Genetics in Medicine Pub Date : 2024-06-25 DOI: 10.1016/j.gim.2024.101197

{"title":"Parents’ and patients’ perspectives, experiences, and preferences for germline genetic or genomic testing of children with cancer: A systematic review","authors":"","doi":"10.1016/j.gim.2024.101197","DOIUrl":"10.1016/j.gim.2024.101197","url":null,"abstract":"<div><h3>Purpose</h3><p>Germline testing in pediatric cancer presents opportunities and challenges. Understanding family perspectives, experiences, and preferences will optimize integration into routine care.</p></div><div><h3>Methods</h3><p>Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched 4 databases for studies exploring perspectives, experiences, and preferences of parents/caregivers and/or patients regarding germline testing of children with cancer. Qualitative and quantitative data were extracted, organized, and summarized by research question and themes.</p></div><div><h3>Results</h3><p>We identified 2286 unique articles, of which 24 were included. Interest in and uptake of testing was high. Families were motivated by altruism and a desire for inheritance/causation information. Testing barriers included psychological concerns, timing of the testing approach if offered at diagnosis or in a high-risk cancer setting and privacy/discrimination. Testing experiences highlighted challenges yet also positive impacts, with results providing psychological relief and informing proactive decision making. Timing preferences varied; however, allowing time to adjust to a new diagnosis was a common theme. Most wanted to receive as many germline sequencing-related results as possible.</p></div><div><h3>Conclusion</h3><p>Findings underscore the importance of integrating germline analyses into pediatric cancer care with flexibility and support for families facing challenges. Where possible, consent should be provided at a time that suits each family’s situation with access to information aligning with their needs and preferences. PROSPERO:CRD42023444890.</p></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467506","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

Errors in genome sequencing result disclosures: A randomized controlled trial comparing neonatology non-genetics healthcare professionals and genetic counselors 基因组测序结果披露错误：新生儿科非遗传学专业医护人员与遗传学顾问的随机对照试验比较。

IF 6.6 1区医学

Genetics in Medicine Pub Date : 2024-06-25 DOI: 10.1016/j.gim.2024.101198

{"title":"Errors in genome sequencing result disclosures: A randomized controlled trial comparing neonatology non-genetics healthcare professionals and genetic counselors","authors":"","doi":"10.1016/j.gim.2024.101198","DOIUrl":"10.1016/j.gim.2024.101198","url":null,"abstract":"<div><h3>Purpose</h3><p>We compared the rate of errors in genome sequencing (GS) result disclosures by genetic counselors (GC) and trained non-genetics healthcare professionals (NGHPs) in SouthSeq, a randomized trial utilizing GS in critically ill infants.</p></div><div><h3>Methods</h3><p>Over 400 recorded GS result disclosures were analyzed for major and minor errors. We used Fisher’s exact test to compare error rates between GCs and NGHPs and performed a qualitative content analysis to characterize error themes.</p></div><div><h3>Results</h3><p>Major errors were identified in 7.5% of disclosures by NGHPs and in no disclosures by GCs. Minor errors were identified in 32.1% of disclosures by NGHPs and in 11.4% of disclosures by GCs. Although most disclosures lacked errors, NGHPs were significantly more likely to make any error than GCs for all result types (positive, negative, or uncertain). Common major error themes include omission of critical information, overstating a negative result, and overinterpreting an uncertain result. The most common minor error was failing to disclose negative secondary findings.</p></div><div><h3>Conclusion</h3><p>Trained NGHPs made clinically significant errors in GS result disclosures. Characterizing common errors in result disclosure can illuminate gaps in education to inform the development of future genomics training and alternative service delivery models.</p></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467505","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

Health-literate care organizations for precision health 有健康知识的护理组织，促进精准健康。

IF 6.6 1区医学

Genetics in Medicine Pub Date : 2024-06-19 DOI: 10.1016/j.gim.2024.101195

引用次数: 0

Weighty matters: Considering the ethics of genetic risk scores for obesity 重要的事情：考虑肥胖遗传风险评分的伦理问题。

IF 6.6 1区医学

Genetics in Medicine Pub Date : 2024-06-18 DOI: 10.1016/j.gim.2024.101196

引用次数: 0

“It’s hard to wait”: Provider perspectives on current genomic care in safety-net NICUs "难以等待"：提供者对安全网新生儿重症监护室当前基因组护理的看法》（Provider Perspectives on Current Genomic Care in Safety-Net NICUs）。

IF 6.6 1区医学

Genetics in Medicine Pub Date : 2024-06-06 DOI: 10.1016/j.gim.2024.101177

{"title":"“It’s hard to wait”: Provider perspectives on current genomic care in safety-net NICUs","authors":"","doi":"10.1016/j.gim.2024.101177","DOIUrl":"10.1016/j.gim.2024.101177","url":null,"abstract":"<div><h3>Purpose</h3><p>Critically ill infants from marginalized populations disproportionately receive care in neonatal intensive care units (NICUs) that lack access to state-of-the-art genomic care, leading to inequitable outcomes. We sought provider perspectives to inform our implementation study (VIGOR) providing rapid genomic sequencing within these settings.</p></div><div><h3>Methods</h3><p>We conducted semistructured focus groups with neonatal and genetics providers at 6 NICUs at safety-net hospitals, informed by the Promoting Action on Research Implementation in Health Services framework, which incorporates evidence, context, and facilitation domains. We iteratively developed codes and themes until thematic saturation was reached.</p></div><div><h3>Results</h3><p>Regarding evidence, providers felt that genetic testing benefits infants and families. Regarding context, the major barriers identified to genomic care were genetic testing cost, lack of genetics expertise for disclosure and follow-up, and navigating the complexity of selecting and ordering genetic tests. Providers had negative feelings about the current status quo and inequity in genomic care across NICUs. Regarding facilitation, providers felt that a virtual support model such as VIGOR would address major barriers and foster family-centered care and collaboration.</p></div><div><h3>Conclusion</h3><p>NICU providers at safety-net hospitals believe that access to state-of-the-art genomic care is critical for optimizing infant outcomes; yet, substantial barriers exist that the VIGOR study may address.</p></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295914","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

Analysis of financial barriers experienced by prospective genetic counseling students 分析未来遗传咨询专业学生遇到的经济障碍。

IF 6.6 1区医学

Genetics in Medicine Pub Date : 2024-06-05 DOI: 10.1016/j.gim.2024.101175

{"title":"Analysis of financial barriers experienced by prospective genetic counseling students","authors":"","doi":"10.1016/j.gim.2024.101175","DOIUrl":"10.1016/j.gim.2024.101175","url":null,"abstract":"<div><h3>Purpose</h3><p>High costs of applying to genetic counseling graduate programs (GCGPs) are likely a barrier to workforce diversification. We sought to determine application costs and assess differences between individuals of historically underrepresented racial and ethnic backgrounds in medicine (hURM) and non-hURM applicants.</p></div><div><h3>Methods</h3><p>Applicants to GCGPs between 2005 to 2020 were surveyed about application history, related expenses, volunteer hours, and financial resources; 383 responses were analyzed.</p></div><div><h3>Results</h3><p>Median total application costs (MTAC) were $2634, $4762, and $5607 (1, 2, and 3 or more application cycles, respectively). Interview-related items (which includes travel) had the highest median cost (1 application cycle: $879). Among those who applied to multiple cycles, hURM respondents had higher MTAC than those of non-hURM ($6713 versus $4762, <em>P</em> = .03) and lower median total volunteer hours (246 versus 381, <em>P</em> = .03). Parental education level differed by hURM status (<em>P</em> = .04). Median financial contribution from parents with and without advanced degrees varied significantly (60% versus 2%, <em>P</em> = .0009).</p></div><div><h3>Conclusion</h3><p>Significant costs are incurred during the GCGP application process, but notable differences in costs and resources were observed between hURM and non-hURM applicants. Stakeholders within the profession should implement strategies to reduce financial barriers and the resulting inequities in the application process.</p></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1098360024001096/pdfft?md5=f54e71c8ac9c64ea336279682b614e38&pid=1-s2.0-S1098360024001096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Breast cancer after ovarian cancer in BRCA1 and BRCA2 pathogenic variant heterozygotes: Lower rates for 5 years post chemotherapy BRCA1 和 BRCA2 致病变异杂合子在卵巢癌后患乳腺癌：化疗后 5 年的发病率较低

IF 6.6 1区医学

Genetics in Medicine Pub Date : 2024-06-03 DOI: 10.1016/j.gim.2024.101172

D. Gareth Evans , Robert D. Morgan , Emma J. Crosbie , Sacha J. Howell , Claire Forde , Anthony Howell , Fiona Lalloo , Emma R. Woodward

{"title":"Breast cancer after ovarian cancer in BRCA1 and BRCA2 pathogenic variant heterozygotes: Lower rates for 5 years post chemotherapy","authors":"D. Gareth Evans , Robert D. Morgan , Emma J. Crosbie , Sacha J. Howell , Claire Forde , Anthony Howell , Fiona Lalloo , Emma R. Woodward","doi":"10.1016/j.gim.2024.101172","DOIUrl":"10.1016/j.gim.2024.101172","url":null,"abstract":"<div><h3>Purpose</h3><p>The identification of germline <em>BRCA1</em>/<em>BRCA2</em> pathogenic variants (PV) infer high remaining lifetime breast/ovarian cancer risks, but there is paucity of studies assessing breast cancer risk after ovarian cancer diagnosis.</p></div><div><h3>Methods</h3><p>We reviewed the history of breast cancer in 895 PV heterozygotes (<em>BRCA1</em> = 541). Cumulative annual breast cancer incidence was assessed at 2, 5, 10, and >10 years after ovarian cancer diagnosis date.</p></div><div><h3>Results</h3><p>Breast cancer annual rates were evaluated in 701 assessable women with no breast cancer at ovarian diagnosis (<em>BRCA1</em> = 425). Incidence was lower at 2 years (1.18%) and 2 to 5 years (1.13%) but rose thereafter for <em>BRCA1</em> with incidence post 10 years in excess of 4% annually. Breast cancer pathology in <em>BRCA1</em> PV heterozygotes showed less high-grade triple-negative breast cancer and more lower-grade hormone-receptor-positive cancer than women with no prior ovarian cancer. In the prospective cohort from ovarian cancer diagnosis, <4% of all deaths were caused by breast cancer, although 50% of deaths in women with breast cancer after ovarian cancer diagnosis were due to breast cancer.</p></div><div><h3>Conclusion</h3><p>Women can be reassured that incidence of breast cancer after ovarian cancer diagnosis is relatively low. It appears likely that this effect is due to platinum-based chemotherapy. Nonetheless women need to be aware that incidence increases thereafter, especially after 10 years.</p></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1098360024001060/pdfft?md5=443938d11216bece9b7dc058dafb8435&pid=1-s2.0-S1098360024001060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141280110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities SREBF2的显性错义变异与复杂的皮肤病、神经和骨骼异常有关

IF 6.6 1区医学

Genetics in Medicine Pub Date : 2024-06-03 DOI: 10.1016/j.gim.2024.101174

{"title":"Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities","authors":"","doi":"10.1016/j.gim.2024.101174","DOIUrl":"10.1016/j.gim.2024.101174","url":null,"abstract":"<div><h3>Purpose</h3><p>We identified 2 individuals with de novo variants in <em>SREBF2</em> that disrupt a conserved site 1 protease (S1P) cleavage motif required for processing SREBP2 into its mature transcription factor. These individuals exhibit complex phenotypic manifestations that partially overlap with sterol regulatory element binding proteins (SREBP) pathway-related disease phenotypes, but <em>SREBF2</em>-related disease has not been previously reported. Thus, we set out to assess the effects of <em>SREBF2</em> variants on SREBP pathway activation.</p></div><div><h3>Methods</h3><p>We undertook ultrastructure and gene expression analyses using fibroblasts from an affected individual and utilized a fly model of lipid droplet (LD) formation to investigate the consequences of <em>SREBF2</em> variants on SREBP pathway function.</p></div><div><h3>Results</h3><p>We observed reduced LD formation, endoplasmic reticulum expansion, accumulation of aberrant lysosomes, and deficits in SREBP2 target gene expression in fibroblasts from an affected individual, indicating that the <em>SREBF2</em> variant inhibits SREBP pathway activation. Using our fly model, we discovered that <em>SREBF2</em> variants fail to induce LD production and act in a dominant-negative manner, which can be rescued by overexpression of S1P.</p></div><div><h3>Conclusion</h3><p>Taken together, these data reveal a mechanism by which <em>SREBF2</em> pathogenic variants that disrupt the S1P cleavage motif cause disease via dominant-negative antagonism of S1P, limiting the cleavage of S1P targets, including SREBP1 and SREBP2.</p></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141278382","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