Genetics in Medicine最新文献

{"title":"X-linked transient antenatal Bartter syndrome related to MAGED2 gene: Enriching the phenotypic description and pathophysiologic investigation","authors":"Alexandre Buffet ,&nbsp;Mathilde Filser ,&nbsp;Alexandra Bruel ,&nbsp;Rodolphe Dard ,&nbsp;Thibaud Quibel ,&nbsp;Charlotte Dubucs ,&nbsp;Theresa Kwon ,&nbsp;Pauline Le Tanno ,&nbsp;Julien Thevenon ,&nbsp;Alban Ziegler ,&nbsp;Lise Allard ,&nbsp;Vincent Guigonis ,&nbsp;Jean-Jacques Roux ,&nbsp;Laurence Heidet ,&nbsp;Claire Rougeulle ,&nbsp;Olivia Boyer ,&nbsp;Rosa Vargas-Poussou ,&nbsp;Marguerite Hureaux","doi":"10.1016/j.gim.2024.101217","DOIUrl":"10.1016/j.gim.2024.101217","url":null,"abstract":"<div><h3>Purpose</h3><div>Transient Bartter syndrome related to pathogenic variants of <em>MAGED2</em> is the most recently described antenatal Bartter syndrome. Despite its transient nature, it is the most severe form of Bartter syndrome in the perinatal period. Our aim was to describe 14 new cases and to try to explain the incomplete penetrance in women.</div></div><div><h3>Methods</h3><div>We report on 14 new cases, including 3 females, and review the 40 cases described to date. We tested the hypothesis that <em>MAGED2</em> is transcriptionally regulated by differential methylation of its CpG-rich promotor by pyrosequencing of DNA samples extracted from fetal and adult leukocytes and kidney samples.</div></div><div><h3>Results</h3><div>Analysis of the data from 54 symptomatic patients showed spontaneous resolution of symptoms in 27% of cases, persistent complications in 41% of cases, and fatality in 32% of cases. Clinical anomalies were reported in 76% of patients, mostly renal anomalies (52%), cardiovascular anomalies (29%), and dysmorphic features (13%). A developmental delay was reported in 24% of patients. Variants were found in all regions of the gene. Methylation analysis of the <em>MAGED2</em> CpG-rich promotor showed a correlation with gender, independent of age, tissue or presence of symptoms, excluding a role for this mechanism in the incomplete penetrance in women.</div></div><div><h3>Conclusion</h3><div>This work enriches the phenotypic and genetic description of this recently described disease and deepens our understanding of the pathophysiological role and regulation of <em>MAGED2</em>. Finally, by describing the wide range of outcomes in patients, this work opens the discussion on genetic counseling offered to families.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 2","pages":"Article 101217"},"PeriodicalIF":6.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733873","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":"Cost-effectiveness of population-wide genomic screening for Lynch Syndrome and polygenic risk scores to inform colorectal cancer screening","authors":"Shangqing Jiang ,&nbsp;Gregory F. Guzauskas ,&nbsp;Shawn Garbett ,&nbsp;John A. Graves ,&nbsp;Marc S. Williams ,&nbsp;Jing Hao ,&nbsp;Jinyi Zhu ,&nbsp;Gail P. Jarvik ,&nbsp;Josh J. Carlson ,&nbsp;Josh F. Peterson ,&nbsp;David L. Veenstra","doi":"10.1016/j.gim.2024.101285","DOIUrl":"10.1016/j.gim.2024.101285","url":null,"abstract":"<div><h3>Purpose</h3><div>Genomic screening to identify individuals with Lynch Syndrome (LS) and those with a high polygenic risk score (PRS) promises to personalize colorectal cancer (CRC) screening. Understanding its clinical and economic impact is needed to inform screening guidelines and reimbursement policies.</div></div><div><h3>Methods</h3><div>We developed a Markov model to simulate individuals over a lifetime. We compared LS+PRS genomic screening with standard of care (SOC) for a cohort of US adults at age 30. The Markov model included health states of no CRC, CRC stages (A-D), and death. We estimated incidence, mortality, and discounted economic outcomes of the population under different interventions.</div></div><div><h3>Results</h3><div>Screening 1000 individuals for LS+PRS resulted in 1.36 fewer CRC cases and 0.65 fewer deaths compared with SOC. The incremental cost-effectiveness ratio was $124,415 per quality-adjusted life year; screening had a 69% probability of being cost-effective using a willingness-to-pay threshold of $150,000/quality-adjusted life year . Setting the PRS threshold at the 90th percentile of the LS+PRS screening program to define individuals at high risk was most likely to be cost-effective compared with 95th, 85th, and 80th percentiles.</div></div><div><h3>Conclusion</h3><div>Population-level LS+PRS screening is marginally cost-effective, and a threshold of 90th percentile is more likely to be cost-effective than other thresholds.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 2","pages":"Article 101285"},"PeriodicalIF":6.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365043","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":"Payer perspectives on genomic testing in the United States: A systematic literature review","authors":"Julie Wiedower ,&nbsp;Hadley Stevens Smith ,&nbsp;Christopher L. Farrell ,&nbsp;Veronica Parker ,&nbsp;Laura Rebek ,&nbsp;Stephanie Clark Davis","doi":"10.1016/j.gim.2024.101329","DOIUrl":"10.1016/j.gim.2024.101329","url":null,"abstract":"<div><h3>Purpose</h3><div>Health care stakeholders’ perspectives on the value of genomic testing vary widely and directly affect the access and practice of genomic medicine. To our knowledge, a review of US health care payers’ perspectives on genomic testing has not been performed.</div></div><div><h3>Methods</h3><div>We conducted a systematic literature review of US payers’ perspectives on genomic testing in the MEDLINE, PubMed, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Of the 161 nonduplicate records screened, we summarized findings from 20 included records, and using the framework method, common domains were recorded.</div></div><div><h3>Results</h3><div>Domains included clinical utility, coverage decision frameworks, potential harms, costs, paying for research, demand/pressure, the flexibility of outcomes considered, and personal utility. There was consensus on the definition of clinical utility as improved health outcomes, and the nuances of genomic testing were reported as challenging to fit within existing coverage decision frameworks. Perspectives varied on accepting broader outcomes or uses of genomic testing and whether costs influence coverage decisions. Study methodologies were heterogeneous.</div></div><div><h3>Conclusion</h3><div>A deeper understanding of how payers approach genomic testing may allow comparison with other stakeholders’ perspectives and may identify challenges, opportunities, and solutions to align a conceptual and evidentiary framework better to demonstrate the value of genomic testing.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 2","pages":"Article 101329"},"PeriodicalIF":6.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667350","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":"Intersectionality in a sociogenomic world: How do race, disability, socioeconomic status, and polygenic prediction interact to affect perceptions of educational trajectories?","authors":"Lucas J. Matthews ,&nbsp;Daphne O. Martschenko ,&nbsp;Colby Lewis V ,&nbsp;Maya Sabatello","doi":"10.1016/j.gim.2025.101368","DOIUrl":"10.1016/j.gim.2025.101368","url":null,"abstract":"<div><h3>Purpose</h3><div>Education is important for lifelong skills and economic growth; however, student placement decisions may be shaped by social biases. As genomic information captured via polygenic scores becomes more available, it may also inform student placement decisions. We assessed the intersectional effects of polygenic scores, race, disability, and socioeconomic status on US adults’ views of educational trajectories using an online experimental survey design.</div></div><div><h3>Methods</h3><div>A total of 1367 US adults were randomized to one of 16 conditions and prompted to read a short vignette about a boy named Michael, also depicted in an image. Each condition varied Michael’s race (Black/White), disability (wheelchair user/no), socioeconomic status (high/low), and polygenic score (high/low) for educational attainment (EA-PGS). After reading the vignette, the respondents were asked to answer multichoice questions about Michael’s immediate and long-term educational trajectories.</div></div><div><h3>Results</h3><div>Variation in Michael’s EA-PGS strongly influenced participants’ expectations regarding (1) the most appropriate immediate educational program for Michael (ie, general, special, or gifted education), (2) whether he would graduate high school, and, if so, (3) the highest educational degree he would complete in his lifetime (associate, bachelor, master, or PhD). Across these responses, high EA-PGS was associated with more socially desirable outcomes, whereas the opposite was true for low EA-PGS. Depicting Michael in a wheelchair significantly influenced respondents’ expectations that his most appropriate immediate educational trajectory would be special. There were significant interactions between Michael’s race, disability, socioeconomic status, and the EA-PGS.</div></div><div><h3>Conclusion</h3><div>Information about children’s EA-PGS may affect their views about their immediate and long-term educational trajectories. The negative effects of low EA-PGS were comparable to those of high EA-PGS. The EA-PGS may be interpreted in ways that compound the existing stereotypes related to a child’s race, disability, and socioeconomic status.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 4","pages":"Article 101368"},"PeriodicalIF":6.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122887","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":"“All doctors should be trained in that”: The coproduction and mixed-methods evaluation of an educational toolkit to enable safe, high-quality genetic health care for people with intellectual disability","authors":"Iva Strnadová ,&nbsp;Manjekah Dunn ,&nbsp;Chloe Molnar ,&nbsp;Julie Loblinzk Refalo ,&nbsp;Jackie Leach Scully ,&nbsp;Joanne Danker ,&nbsp;Michelle Tso ,&nbsp;Tiffany Qing Lim ,&nbsp;Yasmin Cathcart-King ,&nbsp;Karen-Maia Jackaman ,&nbsp;Sarah Hayes ,&nbsp;Sierra Angelina Willow ,&nbsp;Jackie Boyle ,&nbsp;Jennifer Hansen ,&nbsp;Skie Sarfaraz ,&nbsp;Caroline Basckin ,&nbsp;Celia Halliburton ,&nbsp;Thulasee Sri Ganeshan ,&nbsp;Edwina K. Middleton ,&nbsp;Bronwyn Terrill ,&nbsp;Elizabeth Emma Palmer","doi":"10.1016/j.gim.2025.101371","DOIUrl":"10.1016/j.gim.2025.101371","url":null,"abstract":"<div><h3>Purpose</h3><div>People with intellectual disability inequitably access high-quality genetic health care. However, they are keen to understand genetic health care and recommend that clinicians need education on delivering more inclusive care and that multimodal genetic health literacy resources should be coproduced.</div></div><div><h3>Methods</h3><div>Our inclusive research team applied best-practice coproduction principles to deliver a suite of resources, the GeneEQUAL Toolkit. Mixed-methods evaluation, including surveys and focus group/interviews, assessed (1) clinicians’ perceived capabilities, motivation, and opportunities for providing inclusive health care for people with intellectual disability before and after exploring the Toolkit; (2) the perceptions and opinions of people with intellectual disability about the Toolkit; (3) the reach of the Toolkit components; and (4) the reflections of people with intellectual disability and clinicians on the coproduction process.</div></div><div><h3>Results</h3><div>The Toolkit met the expectations and preferences of people with intellectual disability and clinicians, and had a global reach. Coproduction was feasible and judged as critical for the high value of the Toolkit, in motivating clinicians to change their clinical practice and empowering people with intellectual disability.</div></div><div><h3>Conclusion</h3><div>Coproduction can be successfully applied to improve the engagement of people with intellectual disability, potentially reducing health inequity and improving the safety and quality of genetic health care.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 4","pages":"Article 101371"},"PeriodicalIF":6.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074451","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":"De novo variants in RYBP are associated with a severe neurodevelopmental disorder and congenital anomalies","authors":"Monika Weisz-Hubshman ,&nbsp;Lindsay C. Burrage ,&nbsp;Sharayu V. Jangam ,&nbsp;Jill A. Rosenfeld ,&nbsp;Sandra von Hardenberg ,&nbsp;Anke Bergmann ,&nbsp;Manuela Friederike Richter ,&nbsp;Malgorzata Rydzanicz ,&nbsp;Rafal Ploski ,&nbsp;Agnieszka Stembalska ,&nbsp;Wendy K. Chung ,&nbsp;Rebecca R. Hernan ,&nbsp;Foong Y. Lim ,&nbsp;Theresa Brunet ,&nbsp;Steffen Syrbe ,&nbsp;Boris Keren ,&nbsp;Solveig Heide ,&nbsp;David R. Murdock ,&nbsp;Hongzheng Dai ,&nbsp;Fan Xia ,&nbsp;Brendan Lee","doi":"10.1016/j.gim.2025.101369","DOIUrl":"10.1016/j.gim.2025.101369","url":null,"abstract":"<div><h3>Purpose</h3><div>Polycomb group proteins are key epigenetic transcriptional regulators. Multiple neurodevelopmental disorders are associated with pathogenic variants of the genes encoding Polycomb group proteins. RYBP is a core component of the noncanonical Polycomb Repressor Complex 1; however, its role in disease is unclear.</div></div><div><h3>Methods</h3><div>Functional consequences of <em>RYBP</em> variants were assessed using in vitro cellular and in vivo <em>Drosophila melanogaster</em> studies.</div></div><div><h3>Results</h3><div>We described 7 individuals with heterozygous de novo variants of <em>RYBP</em> and their clinical findings, including severe developmental delay, dysmorphisms, and multiple congenital anomalies. We showed that all single-nucleotide variants in <em>RYBP</em> localize to the N-terminal domain of the gene, which encodes the zinc-finger domain and ubiquitin-binding moiety. In vitro studies have demonstrated that the <em>RYBP</em> c.132C&gt;G p.(Cys44Trp) variant causes reduced protein expression but does not affect the binding of YY1, RING1B, or ubiquitin. In vivo overexpression studies in <em>Drosophila melanogaster</em> showed a dramatic functional difference between human RYBP and its variant forms, affecting the C44 amino acid residue. DNA methylation studies suggested a possible episignature associated with <em>RYBP</em>-related disorder.</div></div><div><h3>Conclusion</h3><div>Heterozygous de novo variants in <em>RYBP</em> are associated with an identifiable syndromic neurodevelopmental disorder with multiple congenital anomalies.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 4","pages":"Article 101369"},"PeriodicalIF":6.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074556","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":"Digital technologies in genetic counseling: Recommendations for a morally sound integration","authors":"Marlies N. van Lingen ,&nbsp;Noor A.A. Giesbertz ,&nbsp;Karin R. Jongsma","doi":"10.1016/j.gim.2025.101370","DOIUrl":"10.1016/j.gim.2025.101370","url":null,"abstract":"<div><div>To address the increasing demand for clinical genetic counseling, digital technologies are currently being developed to increase efficiency and overcome logistical and societal barriers in genetic health care. However, it is not self-evident that genetic technologies will improve the quality of and access to genetic counseling. Moreover, several ethical questions about the appropriate tasks of digital technologies in the genetic care process have been raised, particularly when personal contact is supplemented or even replaced with digital technologies. Ethical reflections on the introduction of digital resources in genetic counseling are scarce. Here, we reflect on 3 central domains in which promises of the digitalization of genetic counseling are generally discussed: (1) promoting patient autonomy and patient-centered care, (2) increasing efficiency, and (3) increasing accessibility. We argue that the benefits of digitalization are not self-evident and are paired with challenges. We conclude by offering 4 recommendations to promote the ethically sound development of digital technologies in genetic health care: (1) specify the intended tasks and expected benefits of the digital technology, (2) identify potential challenges of digitalization, (3) consider the role of end users within the genetic care process, and (4) ensure iterative stakeholder consultation and engagement.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 4","pages":"Article 101370"},"PeriodicalIF":6.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074562","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":"Pathogenicity assessment of genetic variants identified in patients with severe hypertriglyceridemia: Novel cases of familial chylomicronemia syndrome from the Dyslipidemia Registry of the Spanish Atherosclerosis Society","authors":"María José Ariza ,&nbsp;Inmaculada Coca-Prieto ,&nbsp;José Rioja ,&nbsp;Ovidio Muñiz-Grijalvo ,&nbsp;Daniel Zambón-Rados ,&nbsp;Agustín Blanco-Echevarría ,&nbsp;Teresa Arrobas-Velilla ,&nbsp;Javier Delgado-Lista ,&nbsp;David León-Jiménez ,&nbsp;Marta Casañas-Martínez ,&nbsp;Luis Antonio Álvarez-Sala ,&nbsp;Liliana Gutiérrez-Carrasquilla ,&nbsp;Justo Sánchez-Gil ,&nbsp;Mónica Domènech ,&nbsp;Andrés González-Jiménez ,&nbsp;María José Benítez-Toledo ,&nbsp;Javier Espíldora-Hernández ,&nbsp;Emilio Ortega-Martínez de Victoria ,&nbsp;Miguel Ángel Sánchez-Chaparro ,&nbsp;Pedro Valdivielso","doi":"10.1016/j.gim.2025.101365","DOIUrl":"10.1016/j.gim.2025.101365","url":null,"abstract":"<div><h3>Purpose</h3><div>Genetic testing is required to confirm a diagnosis of familial chylomicronemia syndrome (FCS). We assessed the pathogenicity of variants identified in the FCS canonical genes to diagnose FCS cases.</div></div><div><h3>Methods</h3><div>245 patients with severe hypertriglyceridemia underwent next-generation sequencing. Preliminary variant pathogenicity criteria and classification, based on the American College of Medical Genetics and Genomics guidelines, were obtained online and verified. Phenotype evaluation was based on lipoprotein lipase activity deficiency, a clinical score, and/or type I hyperlipoproteinemia determined in 25 patients.</div></div><div><h3>Results</h3><div>Twenty-four biallelic variants were analyzed. Evidence-based criteria allowed the reclassification of 8 likely pathogenic (LP) variants in the <em>LPL</em>, <em>APOA5</em>, and <em>LMF1</em> genes into pathogenic (P) and the change of 2 variants of uncertain significance (VUS) to LP. Conversely, 2 variations in <em>LMF1</em> remained as VUS. Additionally, 1 variant in <em>LPL</em> and 2 in <em>GPIHBP1</em> were likely benign. Twenty FCS cases had biallelic P/LP variants and 1 patient, with an FCS phenotype, harbored biallelic VUS. FCS was excluded from 4 patients with pathogenic/likely benign combinations.</div></div><div><h3>Conclusion</h3><div>The analysis of the clinical and biochemical features of patients with variants in the FCS canonical genes allowed a confident variant classification that helped in the diagnosis of novel FCS cases.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 5","pages":"Article 101365"},"PeriodicalIF":6.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052332","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":"Newborn screening for common genetic variants associated with permanent hearing loss: Implementation in Ontario and review of the first 3 years","authors":"Kristin D. Kernohan ,&nbsp;Lauren Gallagher ,&nbsp;Marie Pigeon ,&nbsp;Ed Yeh ,&nbsp;Melanie Lacaria ,&nbsp;Michelle M. Axford ,&nbsp;Johnna MacCormick ,&nbsp;Vicky Papaioannou ,&nbsp;Nada Quercia ,&nbsp;Charles Rupar ,&nbsp;Kim Zimmerman ,&nbsp;Stacey Weber ,&nbsp;Sharon L. Cushing ,&nbsp;Pranesh Chakraborty","doi":"10.1016/j.gim.2025.101364","DOIUrl":"10.1016/j.gim.2025.101364","url":null,"abstract":"<div><h3>Purpose</h3><div>Early hearing detection and intervention (EHDI) programs using audiometric screening techniques alone have a limited ability to detect noncongenital childhood permanent hearing loss (PHL). In 2019, Ontario launched universal newborn screening (NBS) for PHL risk factors, including congenital cytomegalovirus and 22 common variants in <em>GJB2</em> and <em>SLC26A4</em>. Here, we describe our experience in screening for genetic risk factors.</div></div><div><h3>Methods</h3><div>Ontario newborns who participated in universal newborn hearing screening (UNHS) were offered risk factor screening using dried blood spots (DBS) collected for conventional newborn screening. The screening was conducted using a custom MassArray assay, and positive results were confirmed by Sanger sequencing or polymerase chain reaction. Diagnostic audiological assessments were performed for all screen-positive infants.</div></div><div><h3>Results</h3><div>Of the 412,424 infants screened, 93 had 2 variants in <em>GJB2</em> or <em>SLC26A4.</em> Of these<em>,</em> 72 had confirmed PHL, 20 had normal hearing, and 1 declined follow-up. Thirteen infants with PHL (1 in 31,724; 11.8% of screen positives) were not identified through audiometric testing as they passed (3) or missed (10) the screening. Importantly, among infants who ultimately received cochlear implants, the detection of genetic etiology through NBS led to an accelerated time to diagnosis, assessment, and intervention.</div></div><div><h3>Conclusion</h3><div>Genetic screening has strengthened UNHS and care for infants with or at risk of PHL in Ontario. This study is a step toward the broader inclusion of genomic testing in NBS.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 4","pages":"Article 101364"},"PeriodicalIF":6.6,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023211","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":"Genomic sequencing in diverse and underserved pediatric populations: Parent perspectives on understanding, uncertainty, psychosocial impact, and personal utility of results","authors":"Barbara B. Biesecker ,&nbsp;Sara L. Ackerman ,&nbsp;Kyle B. Brothers ,&nbsp;Kelly M. East ,&nbsp;Ann Katherine M. Foreman ,&nbsp;Lucia A. Hindorff ,&nbsp;Carol R. Horowitz ,&nbsp;Gail P. Jarvik ,&nbsp;Sara J. Knight ,&nbsp;Michael C. Leo ,&nbsp;Donald L. Patrick ,&nbsp;Christine Rini ,&nbsp;Jill O. Robinson ,&nbsp;Nuriye Nalan Sahin-Hodoglugil ,&nbsp;Anne Slavotinek ,&nbsp;Sabrina A. Suckiel ,&nbsp;David L. Veenstra ,&nbsp;Randi E. Zinberg ,&nbsp;Jessica Ezzell Hunter","doi":"10.1016/j.gim.2025.101363","DOIUrl":"10.1016/j.gim.2025.101363","url":null,"abstract":"<div><h3>Purpose</h3><div>Limited evidence evaluates parents’ perceptions of their child’s clinical genome-scale sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap.</div></div><div><h3>Methods</h3><div>Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure. We assessed outcomes’ associations with child- and parent-related factors: child age; type of GS finding; and parent health literacy, numeracy, and education.</div></div><div><h3>Results</h3><div>A total of 1763 parents completed surveys; 83% met “underserved” criteria based on race, ethnicity, and risk factors for barriers to access. We observed high perceived understanding and personal utility and low test-related distress. Outcomes were associated with the type of GS finding; parents of children with a pathogenic or likely pathogenic finding endorsed higher personal utility and more test-related distress than those whose children had a variant of uncertain significance or normal finding. Personal utility was higher in parents who met the criteria for “underserved.”</div></div><div><h3>Conclusion</h3><div>Our findings shed light on correlates of parents’ cognitive and emotional responses to their child’s GS findings and emphasize the need for tailored support in disclosure discussions.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 4","pages":"Article 101363"},"PeriodicalIF":6.6,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023197","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}