Genetics in Medicine最新文献

{"title":"How do parents decide on genetic testing in pediatrics? A systematic review","authors":"Elena Sophia Doll ,&nbsp;Seraina Petra Lerch ,&nbsp;Katja Maria Schmalenberger ,&nbsp;Karla Alex ,&nbsp;Stefan Kölker ,&nbsp;Heiko Brennenstuhl ,&nbsp;Stacey Pereira ,&nbsp;Hadley Smith ,&nbsp;Eva Caroline Winkler ,&nbsp;Julia Mahal ,&nbsp;Beate Ditzen","doi":"10.1016/j.gim.2025.101390","DOIUrl":"10.1016/j.gim.2025.101390","url":null,"abstract":"<div><h3>Purpose</h3><div>This systematic review aims to identify the factors that influence parents’ decisions regarding pediatric diagnostic genetic testing (DT) and predictive genetic testing (PT). These factors are integrated into a conceptual decision-making model. Implications for genetic counseling, research, and ethics were derived.</div></div><div><h3>Methods</h3><div>PubMed, PsychInfo, WebofScience, and related references were searched for original publications between 2000 and 2023. The extracted factors were categorized using existing models.</div></div><div><h3>Results</h3><div>Of the 5843 publications, 56 met the inclusion criteria. The included studies differentiated between DT, traditional PT, and expanded PT and described factors affecting parental decisions to have the child genetically tested and to be informed about additional findings. Factors included (1) benefits/hopes, (2) worries/concerns, (3) values and beliefs, (4) individual circumstances, and (5) emotional states.</div></div><div><h3>Conclusion</h3><div>Our work extends the existing empirical decision model of family decisions about genome sequencing to genetic testing in pediatrics in general, adding the categories of individual circumstances and emotional states. These factors can be further integrated into the Health Belief Model; the importance of emotional states is reflected in dual-process theories, such as the Fuzzy Trace Theory. Research is required on emotional states, differences between DT and PT, parents’ decisions regarding result disclosure, and dyadic variables as decision-making predictors.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 5","pages":"Article 101390"},"PeriodicalIF":6.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482968","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}

{"title":"Parents’ perceptions of the utility of genetic testing in the NICU","authors":"Katharine Press Callahan ,&nbsp;Rebecca Mueller ,&nbsp;Steven Joffe ,&nbsp;Cara Skraban ,&nbsp;Nancy B. Spinner ,&nbsp;Karen Crew ,&nbsp;Justin Clapp ,&nbsp;David Munson ,&nbsp;Chris Feudtner","doi":"10.1016/j.gim.2025.101393","DOIUrl":"10.1016/j.gim.2025.101393","url":null,"abstract":"<div><h3>Purpose</h3><div>Although several studies have evaluated the perspectives of parents in the neonatal intensive care unit on the utility of genetic testing in a research context and concluded with a positive appraisal, some data point to more varied perceptions.</div></div><div><h3>Methods</h3><div>Semistructured interviews were conducted to elicit parental beliefs about the ways in which clinical (nonresearch) genetic testing could be both helpful and harmful.</div></div><div><h3>Results</h3><div>We interviewed 43 parents of 36 neonates who were recommended and either accepted or declined to participate in clinical genetic testing. Parents described 5 types of problems they believed genetic information may address, what we term problem-solving contexts: treatment, coping, parenting, prognostic, and existential contexts. Most parents consider multiple problem-solving contexts when assessing benefits, which frequently results in ambivalence.</div></div><div><h3>Conclusion</h3><div>Parents in the neonatal intensive care unit appear to be more ambivalent about the utility of genetic information than has been reflected in most recent studies. This discrepancy is likely related to our sample population, clinical rather than research methodology, which encouraged parents to discuss contexts beyond the medical field. Our findings suggest that informed pretest consent discussions and posttest counseling should encourage parents to discuss multiple problem-solving contexts. Researchers should also find ways to incorporate multiple contexts and diverse perspectives into their utility measures.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 6","pages":"Article 101393"},"PeriodicalIF":6.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482969","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}

{"title":"ClinGen recuration of hearing loss-associated genes demonstrates significant changes in gene-disease validity over time","authors":"Kezang C. Tshering ,&nbsp;Marina T. DiStefano ,&nbsp;Andrea M. Oza ,&nbsp;Pamela Ajuyah ,&nbsp;Ryan Webb ,&nbsp;Enyonam Edoh ,&nbsp;Ellie Broeren ,&nbsp;Julie Ratliff ,&nbsp;Vanessa Gitau ,&nbsp;Kelley Paris ,&nbsp;Amal Aburyyan ,&nbsp;John Alexander ,&nbsp;Victoria Albano ,&nbsp;Donglin Bai ,&nbsp;Kevin T.A. Booth ,&nbsp;Paula I. Buonfiglio ,&nbsp;Cherine Charfeddine ,&nbsp;Viviana Dalamón ,&nbsp;Ignacio del Castillo ,&nbsp;Miguel Angel Moreno-Pelayo ,&nbsp;Zubair Ahmed","doi":"10.1016/j.gim.2025.101392","DOIUrl":"10.1016/j.gim.2025.101392","url":null,"abstract":"<div><h3>Purpose</h3><div>The Clinical Genome Resource (ClinGen) Hearing Loss Gene Curation Expert Panel was assembled in 2016 and has since curated 174 gene-disease relationships (GDRs) using ClinGen’s semiquantitative framework. ClinGen mandates the timely recuration of all GDRs classified as Disputed, Limited, Moderate, and Strong every 2 to 3 years.</div></div><div><h3>Methods</h3><div>Thirty-five GDRs met the criteria for recuration within 2 years of original curation. Previous evidence was reevaluated using the latest curation guidelines, and a comprehensive literature review was performed to obtain new evidence. Recurations were approved by the Gene Curation Expert Panel and published on the ClinGen website (<span><span>www.clinicalgenome.org</span><svg><path></path></svg></span>).</div></div><div><h3>Results</h3><div>Eight of 35 GDRs (22%) changed their classification. Two Moderate and 5 Strong GDRs were upgraded to Definitive because of new case evidence. One Strong was subsumed under another Definitive GDR after evaluation of the lumping/splitting of disease entities. Twenty-seven of 35 patients remained unchanged, with little to no new evidence reported.</div></div><div><h3>Conclusion</h3><div>Genes classified as Moderate and Strong were likely to build evidence and change their classification over time, whereas Limited were unlikely to gain evidence. These findings highlight the critical role of recuration in ensuring that genetic tests and research studies incorporate the most recent evidence into their efforts.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 5","pages":"Article 101392"},"PeriodicalIF":6.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482967","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}

{"title":"DICER1 in pediatric and adult cancer predisposition populations: Prevalence, phenotypes, and mosaicism","authors":"Lluis Salvador ,&nbsp;Jesús del Valle ,&nbsp;Eduard Dorca ,&nbsp;Anne-Sophie Chong ,&nbsp;Anne-Laure Chong ,&nbsp;José Camacho Valenzuela ,&nbsp;Elisabet Munté ,&nbsp;Cristina Rioja ,&nbsp;Laura Martí-Sánchez ,&nbsp;Mónica Salinas ,&nbsp;Esther Darder ,&nbsp;Marc R. Fabian ,&nbsp;Joan Brunet ,&nbsp;Hector Salvador ,&nbsp;Conxi Lázaro ,&nbsp;Barbara Rivera","doi":"10.1016/j.gim.2025.101385","DOIUrl":"10.1016/j.gim.2025.101385","url":null,"abstract":"<div><h3>Purpose</h3><div>DICER1 tumor predisposition syndrome (DTPS) is a hereditary condition affecting children and young adults. Identification of <em>DICER1</em> carriers is key for prevention and actionability in families. However, DTPS diagnosis is hindered by its incomplete penetrance and broad phenotypic spectrum.</div></div><div><h3>Methods</h3><div>We performed an analysis of <em>DICER1</em> sequencing data from 92 children and 6108 adults with suspected cancer predisposition syndrome. Clinical and <em>DICER1</em> somatic data from selected carriers and public data sets were studied.</div></div><div><h3>Results</h3><div>The prevalence of germline <em>DICER1</em> pathogenic variants was 1:30 in children and 1:3054 in adults. No adult referral phenotype was a known DTPS-associated tumor, although 3 of 5 carriers developed thyroid alterations. We provide functional evidence supporting the pathogenicity of a novel in-frame deletion. A 56-year-old woman with ovarian carcinoma and toxic diffuse thyroid hyperplasia was found to have a postzygotic hotspot missense variant.</div></div><div><h3>Conclusion</h3><div>The prevalence of <em>DICER1</em> pathogenic variants in cancer predisposition populations was 5 to 6 times that reported in the general population. Pediatric-onset DTPS is well characterized, whereas adult carriers mainly present with thyroid abnormalities in the absence of DICER1-related family history, thus requiring accurate criteria for its identification when in constellation with other tumor types. Postzygotic hotspot missense variants may exist without the expected severe phenotype.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 5","pages":"Article 101385"},"PeriodicalIF":6.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457534","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}

{"title":"Patterns of X-linked inheritance: a new approach for the genome era.","authors":"Sanjana Basava, Charles J Billington, Laura Carrel, Leslie G Biesecker, William B Dobyns","doi":"10.1016/j.gim.2025.101384","DOIUrl":"https://doi.org/10.1016/j.gim.2025.101384","url":null,"abstract":"<p><p>The concepts of X-linked (XL) \"dominant\" and \"recessive\" inheritance originated long before dosage compensation for X chromosome genes was understood, but now have no scientific basis. To address continuing misunderstanding of XL inheritance in humans we reviewed data on penetrance, expressivity, and X chromosome inactivation for 55 XL genes and 57 XL disorders. Our analysis demonstrated widely varying penetrance in heterozygous females and variations in the patterns of inheritance based on the degree of cell selection, severity of the phenotype in males, cell autonomous or non-cell autonomous function of the gene product, and other factors. We propose four new groups of XL disorders with variations in the pattern of inheritance and recommend that the biologically flawed concepts of XL \"dominant\" and \"recessive\" inheritance for humans and other therian mammals be retired.</p>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":" ","pages":"101384"},"PeriodicalIF":6.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440638","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}

{"title":"Mainstreaming improved adoption of germline testing for Veterans Affairs patients with metastatic prostate cancer without exacerbating disparities.","authors":"Maren T Scheuner, Katherine J Hoggatt, Paloma Sales, Barbara Lerner, Eva Ferino, Morgan Danowski, Ning Zhang, Colin Purmal, Samuel L Washington, Michael M Goodman, Emily E Ziegler, Andrea J Stoddard, Carolyn Menendez, Tori Foote, Kerry Rowe, Gina McWhirter, Michael J Kelley","doi":"10.1016/j.gim.2025.101383","DOIUrl":"10.1016/j.gim.2025.101383","url":null,"abstract":"<p><strong>Purpose: </strong>To improve germline testing adoption for Veterans Affairs patients with metastatic prostate cancer (mPrCA), new delivery models were introduced to complement genetic consultation (traditional model), including mainstreaming where oncologists perform pre/posttest activities and a hybrid model where oncologists perform informed consent and then refer to genetics. We assessed germline testing adoption by delivery model.</p><p><strong>Methods: </strong>We conducted a nationwide cohort study of mPrCA patients ascertained from May 3, 2021, to November 2, 2022, with follow-up through May 3, 2023. We assessed associations between patient and facility characteristics and having or completing germline test orders using Cox proportional hazards models.</p><p><strong>Results: </strong>We identified 18,623 mPrCA patients. The average age was 73.9 years (SD, 8.3; range 35-102) with 59.6% non-Hispanic White and 28.9% non-Hispanic Black patients. The cumulative incidence of germline test orders was 13.7% over 2 years. Non-Hispanic Black patients were more likely than non-Hispanic White patients to have germline test orders (hazard ratio [HR], 1.28; 95% CI, 1.15-1.41) but less likely to complete their orders (HR, 0.81; 95% CI 0.72-0.91). Compared with non-Hispanic White patients, non-Hispanic Black patients were more likely to complete orders under the traditional model (HR, 1.40; 95% CI, 111-1.76), less likely under the hybrid model (HR, 0.62; 95% CI, 0.50-0.77) with no difference under the mainstream model.</p><p><strong>Conclusion: </strong>Mainstreaming germline testing for mPrCA patients improved adoption without introducing disparities between non-Hispanic Black and White patients.</p>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":" ","pages":"101383"},"PeriodicalIF":6.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440636","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}

{"title":"AUTS2-related syndrome: Insights from a large European cohort","authors":"Lorenzo Loberti ,&nbsp;Loredaria Adamo ,&nbsp;Enrica Antolini ,&nbsp;Giulia Casamassima ,&nbsp;Anne Destrèe ,&nbsp;Nicola Brunetti-Pierri ,&nbsp;David Genevieve ,&nbsp;Philippe Christophe ,&nbsp;Christine Coubes ,&nbsp;Hilde Van Esch ,&nbsp;Theresia Herget ,&nbsp;Fanny Kortüm ,&nbsp;Jasmin Lisfeld ,&nbsp;Anna Charlotte Möllring ,&nbsp;Martin Zenker ,&nbsp;Jonathan Levy ,&nbsp;Laurence Perrin ,&nbsp;Anne-Claude Tabet ,&nbsp;Anna Maruani ,&nbsp;Arthur Sorlin ,&nbsp;Anna Maria Pinto","doi":"10.1016/j.gim.2025.101375","DOIUrl":"10.1016/j.gim.2025.101375","url":null,"abstract":"<div><h3>Purpose</h3><div><em>AUTS2</em>-related syndrome is characterized by developmental delay, autism spectrum disorder, and intellectual disability. From alternative promoters, <em>AUTS2</em> encodes 2 distinct long and short isoforms encoding a putative transcriptional activator.</div></div><div><h3>Methods</h3><div>Through a European collaborative study, we collected clinical and genotype data on the largest <em>AUTS</em><em>2</em>-related syndrome cohort of 58 patients harboring genomic rearrangements or single-nucleotide variants (SNVs).</div></div><div><h3>Results</h3><div>Pathogenic SNVs were recurrently found in individuals from different countries, suggesting mutational hotspots. Independent of the underlying defect at the <em>AUTS2</em> locus, we observed that autistic behavior, hyperactivity, learning difficulties, and speech delay are common features of <em>AUTS2</em>-related syndrome. Among patients with SNVs, individuals carrying pathogenic variants affecting both longer and shorter <em>AUTS2</em> transcripts showed a recognizable phenotype with microcephaly, brachycephaly, microretrognathia, broad nasal base, and anteverted nares. Behavioral disorders were more common in patients with variants affecting only the longer isoform. Arthrogryposis and stiff movements were only observed in patients with SNVs.</div></div><div><h3>Conclusion</h3><div>This study provides a comprehensive clinical characterization of <em>AUTS2</em>-related syndrome, reveals few genotype-phenotype correlations, and suggests that the disruption of the 2 distinct <em>AUTS2</em> transcripts has a different impact on the clinical phenotype.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 6","pages":"Article 101375"},"PeriodicalIF":6.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425271","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}

{"title":"Monogenic disorders associated with motor speech phenotypes in children and adolescents undergoing clinical exome sequencing","authors":"Marissa W. Mitchel ,&nbsp;Matthew Oetjens ,&nbsp;Alexander S.F. Berry ,&nbsp;Alicia Johns ,&nbsp;Andrés Moreno-De-Luca ,&nbsp;Rebecca I. Torene ,&nbsp;Natasha T. Strande ,&nbsp;Marina T. DiStefano ,&nbsp;Lindsay Havens Dyer ,&nbsp;Tracy Brandt ,&nbsp;Brenda M. Finucane ,&nbsp;David H. Ledbetter ,&nbsp;Kyle Retterer ,&nbsp;Christa L. Martin ,&nbsp;Scott M. Myers","doi":"10.1016/j.gim.2025.101374","DOIUrl":"10.1016/j.gim.2025.101374","url":null,"abstract":"<div><h3>Purpose</h3><div>Prior studies investigating the genetic architecture of pediatric motor speech disorders (MSDs) have been limited by small sample sizes and an exclusive focus on apraxia. We aimed to identify pathogenic genomic variants associated with MSDs in a large pediatric population referred for exome sequencing (ES).</div></div><div><h3>Methods</h3><div>We identified pediatric patients with MSDs who had clinical ES between 2012 and 2022. The rate of pathogenic/likely pathogenic (P/LP) findings considered causative of the MSD phenotype was determined and delineated by sex and neurodevelopmental comorbidity. Gene-based burden testing compared the rate of P/LP variants in each gene in MSD cases with a comparison clinical ES cohort.</div></div><div><h3>Results</h3><div>Positive diagnostic results were detected in 527 of 2004 (26.3%) patients with MSDs, with higher diagnostic rates in females and individuals with neurodevelopmental comorbidities. P/LP sequence variants were detected in 262 genes. Gene-based case-referent burden analysis revealed that 30 genes were nominally associated with MSDs, 2 of which (<em>SETBP1</em> and <em>ADCY5</em>) survived exome-wide correction.</div></div><div><h3>Conclusion</h3><div>Over 25% of patients with MSDs were found to harbor P/LP variants in 262 genes, many of which have not previously been associated with MSDs. Potential clinical implications include early implementation of intensive speech therapy for children diagnosed with monogenic causes of MSDs.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 4","pages":"Article 101374"},"PeriodicalIF":6.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390719","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}

{"title":"Efficacy of transitioning from alglucosidase alfa to avalglucosidase alfa in infantile-onset Pompe disease: A single-center cohort analysis","authors":"Yin-Hsuan Chien ,&nbsp;Hui-An Chen ,&nbsp;Rai-Hseng Hsu ,&nbsp;Chien-Hua Yeh ,&nbsp;Ching-Ya Fang ,&nbsp;Ni-Chung Lee ,&nbsp;Wuh-Liang Hwu ,&nbsp;Yin-Hsiu Chien","doi":"10.1016/j.gim.2025.101373","DOIUrl":"10.1016/j.gim.2025.101373","url":null,"abstract":"<div><h3>Purpose</h3><div>Although alglucosidase alfa (AGL) is the standard treatment for Pompe disease, its efficacy is limited, partially because of its low mannose-6-phosphate content. Avalglucosidase alfa (AVA), a glycoengineered recombinant human acid α-glucosidase, has shown improved receptor-mediated uptake compared with AGL. Herein, we report the long-term efficacy and safety of AVA in patients with infantile-onset Pompe disease (IOPD) previously treated with AGL.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included 9 patients with IOPD who transitioned from AGL to AVA; these patients were diagnosed and treated after being detected with IOPD via newborn screening. We analyzed the clinical status, biomarker levels (serum creatine kinase and urine glucose tetrasaccharide), and functional assessments before and after AVA treatment of these patients. Statistical analyses were performed using the Wilcoxon matched-pair signed-rank test.</div></div><div><h3>Results</h3><div>Due to inadequate responses, all 9 patients received AGL at dosages exceeding the label recommendations, including one who also had tried cipaglucosidase alfa plus miglustat before transitioning to AVA. After transitioning to AVA at a dosage of 40 mg/kg every other week for a median duration of 4.9 years, the patients experienced significant reductions in biomarker levels (serum creatine kinase levels decreased by 63% and urine glucose tetrasaccharide levels decreased by 69%). Functional assessments, including pulmonary function and 6-minute walk tests, showed improvement in young patients but remained stable in older patients. Safety analyses revealed manageable infusion-associated reactions. Immune modulation therapy for antidrug antibodies was administered to 1 IOPD patient.</div></div><div><h3>Conclusion</h3><div>The transition from a high dose of AGL to AVA demonstrated sustained improvements in biomarker levels and motor function in patients with IOPD. Early initiation of AVA is crucial for patients with IOPD.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 5","pages":"Article 101373"},"PeriodicalIF":6.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382228","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}

{"title":"Feasibility of using patient navigation to improve identification of hereditary cancer syndromes in newly diagnosed patients with colorectal cancer","authors":"Emma Sears ,&nbsp;Jacky Dahlquist ,&nbsp;Sarah Stayman ,&nbsp;Cynthia Ko ,&nbsp;Eric Q. Konnick ,&nbsp;Allison Cole ,&nbsp;Ying Zhang ,&nbsp;Marlana Kohn ,&nbsp;Vida Henderson ,&nbsp;Sarah Knerr","doi":"10.1016/j.gim.2025.101372","DOIUrl":"10.1016/j.gim.2025.101372","url":null,"abstract":"<div><h3>Purpose</h3><div>Germline genetic testing to identify hereditary cancer syndromes in patients newly diagnosed with colorectal cancer (CRC) carries substantial benefits. We examined the feasibility of using patient navigation, an evidence-based approach to reduce structural barriers to recommended care, to improve test completion by increasing pretest counseling attendance.</div></div><div><h3>Methods</h3><div>We conducted key informant interviews with representatives from organizations providing cancer care to CRC patients. Interviews included questions derived from the Consolidated Framework for Implementation Research, which delineates barriers and facilitators to implementing evidence-based practices. We used an inductive-deductive coding approach to identify themes related to program feasibility.</div></div><div><h3>Results</h3><div>We interviewed 19 participants across 13 organizations. Key feasibility barriers included funding to implement and sustain a navigation program, staffing and supervising the navigator role, health information technology needs, gaining administrators’ buy-in, and evolving genetic service delivery models. Participants suggested multiple strategies to address implementation barriers, but most would prefer other approaches to improve genetic test completion over implementing a genomics-focused patient navigation program.</div></div><div><h3>Conclusion</h3><div>Stakeholders across a range of health care organizations saw limited value in improving the identification of hereditary CRC syndromes by implementing a program designed to increase pretest genetic counseling attendance. The need to scale up genetic testing has shifted interest toward delivery models better integrated in established care pathways, requiring fewer resources and providing broader reach.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 5","pages":"Article 101372"},"PeriodicalIF":6.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382232","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}