European Journal of Human Genetics最新文献

{"title":"Healthcare professionals' views on expanding newborn screening with or without genomics in France: Results of the SeDeN-p2 study.","authors":"Camille Level, Frédéric Huet, Dominique Salvi, Christel Thauvin Robinet, Emmanuel Simon, Margot Lemaitre, Christine Peyron, Laurence Faivre","doi":"10.1038/s41431-026-02250-3","DOIUrl":"https://doi.org/10.1038/s41431-026-02250-3","url":null,"abstract":"<p><p>Therapeutic advances and the rapid, cost-effective development of next-generation sequencing (NGS) have increased interest in expanding newborn screening (NBS) through genomics. The SeDeN-p2 study assessed the acceptability among healthcare professionals in France, of expanding NBS, particularly with genetics as a first-line test, by examining areas of convergence and divergence in their expectations. A national cross-sectional survey was conducted between June and December 2021 via professional networks and learned societies involved in NBS and genetics, in partnership with the French Society of Newborn Screening. The questionnaire comprised 101 closed-ended and 14 open-ended questions. After data cleaning, 1077 responses were analysed. Respondents were mainly paediatricians (43%), gynaecologists or midwives (36%), and medical geneticists or genetic counsellors (17%). Support for the inclusion of treatable childhood-onset conditions was very high, with over 95% endorsing their integration into NBS, although 29% still considered the current NBS programme sufficient. Views varied substantially by specialty, particularly regarding the scope of conditions and the use of NGS. Genetics professionals were more conservative, especially concerning variants with limited actionability, organisational constraints, and interpretive uncertainty, while midwives and gynaecologists were generally more favourable. Convergence was strongest for treatable paediatric conditions and shared ethical concerns, notably data misuse, psychosocial burden, and the child's future autonomy. The need for improved communication with families was widely emphasised. The SeDeN-p2 study shows strong but conditional support among French healthcare professionals for integrating genetics into NBS, providing key insights to inform future policy and practice.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic pathways in developmental disorders: a decade-apart comparison of two multicenter cohorts (2012-2022).","authors":"Julien Maraval, Céline Dampfhoffer, Antoine Journé, Céline Poitevin, Marie Laure Asensio, Niki Sabour, Anne-Sophie Briffaut, Didier Lacombe, Marta Spodenkiewicz, David Genevieve, Olivier Patat, Camille Cenni, Philippe Khau Van Kien, Laëtitia Lambert, Mathilde Renaud, Hortense Thomas, Céline Poirsier, Elise Schaefer, Juliette Piard, Yline Capri, Rodolphe Dard, Cyril Mignot, André Delahaye-Duriez, Marilyn Lackmy, Sylvie Odent, Annick Toutain, Marie-Line Jacquemont, Bertrand Isidor, Dominique Bonneau, Séverine Audebert-Bellanger, Radka Stoeva, Florence Demurger, Odile Boute, Cindy Colson, Florence Jobic, Bénédicte Deemer, Anne-Marie Guerrot, Aline Vincent-Devulder, Pauline Monin, Sabine Sigaudy, Mathieu Milh, Isabelle Marey, Christine Francannet, Fanny Laffargue, Renaud Touraine, Maude Grelet, Gwenaël Le Guyader, Matthieu Egloff, Frédéric Bilan, Jeanne Amiel, Caroline Racine, Christine Vinciguera, Pierre Blanc, Christel Thauvin-Robinet, Laurent Demougeot, Aurore Pélissier, Estelle Colin, Christine Binquet, Laurence Faivre","doi":"10.1038/s41431-026-02242-3","DOIUrl":"https://doi.org/10.1038/s41431-026-02242-3","url":null,"abstract":"<p><p>As part of the third French National Plan for Rare Diseases, the AnDDI-Rares network initiated a nationwide study in 2019 to assess how diagnostic practices for developmental anomalies have evolved over the last decade (2012-2022), in the context of the implementation of genome sequencing (GS) capabilities via the France Genomic Medicine Plan. We analyzed diagnostic rates in 34 French centers for developmental diseases, comparing a randomly selected week in 2012 with one in 2022. Secondary outcomes were diagnostic delays and GS efficiency. A total of 430 patients were identified in 2012 and 551 in 2022, a 28% increase in activity. The overall diagnostic yield rose from 16% in 2012 to 27% in 2022 (p < 0.001), in parallel with the increased use of next-generation sequencing (NGS) approaches, and the shift from targeted gene panels toward GS. Among previously undiagnosed patients from the 2012 cohort who pursued further investigations, NGS enabled additional diagnoses with GS showing a high diagnostic yield (42%) in individuals with longstanding diagnostic odysseys. Significant heterogeneity in strategies persisted, highlighting the impact of, and unequal access to GS across centers. These results highlight advancements in diagnostic practices and the pivotal role of Next-Generation Sequencing. Nonetheless, unequal access, attrition, and limited uptake of renewed investigations reveal persistent barriers. Continuous patient engagement and coordinated efforts are required to promote GS-first approaches and ensure equitable access across the healthcare system.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient harms during delayed access to clinical genetics services. A systematic literature review and synthesis without meta-analysis (SWiM).","authors":"Michaela Cormack, Janet Long, Alan Ma, Nabila Binte Haque, Maryam Vizheh, Amanda Springer, Mary Simons, Peter Hibbert, Jeffrey Braithwaite","doi":"10.1038/s41431-026-02247-y","DOIUrl":"https://doi.org/10.1038/s41431-026-02247-y","url":null,"abstract":"<p><p>Delays in accessing clinical genetics services are increasing globally. This systematic review and Synthesis Without Meta-analysis investigated the types and frequency of harms during delayed access to clinical genetics services (PROSPERO CRD42024601622). We searched peer-reviewed literature across multiple databases and included Australian policies, white papers and government documents reporting patient harms. Certainty of evidence was assessed using GRADE. Five studies met inclusion criteria. The clearest signal was non-attendance, which rose with longer waits across two studies (n = 1280). Martinez et al. observed mortality among clinical genetics waiting-list patients. Oncology and other tertiary specialties with higher mortality risk are commonly referred to clinical genetics. A randomised trial (n = 590) of cancer genetics patients found psychological distress during waiting, with high baseline distress persisting despite intervention. A large cohort (n = 48,622) reported family-level harms, including deaths among at-risk relatives. Certainty was moderate for non-attendance and very low for mortality, distress and family harms due to limited studies and imprecision. Direct causal evidence and significant associations linking waiting time delays to harm remain sparse; this represents a significant gap in the evidence base. Better evidence on presentations and factors linked to harm would support more effective waiting-list management. This review characterises the types of harm experienced by patients during the clinical genetics waiting period, providing a foundation for future investigation and demonstrating opportunity for improved services. System-level action is needed, including safety evaluation of emerging models of care, structured prioritisation, improved genetics literacy and transparent waiting-list management to strengthen equity and safety.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomics cycle: discover, diagnose, interpret, act","authors":"Seda S. Zonuzi","doi":"10.1038/s41431-026-02251-2","DOIUrl":"10.1038/s41431-026-02251-2","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"34 10","pages":"1415-1416"},"PeriodicalIF":4.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-026-02251-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterising the 'Genomics Friend': Experiences of learning genomics in the workplace to inform implementation efforts.","authors":"Alice Kim, Jennifer Weller-Newton, Louise Keogh, Amy Nisselle","doi":"10.1038/s41431-026-02245-0","DOIUrl":"https://doi.org/10.1038/s41431-026-02245-0","url":null,"abstract":"<p><p>Large-scale genomic medicine implementation efforts are presenting relevant and authentic opportunities for the health workforce to learn genomics in the workplace, particularly from genomic expert colleagues or 'champions'. This paper presents novel insights on genomic experts' role and influence on learning genomics from the perspective of physicians not trained in genetics. As part of a study on workplace learning of genomics, longitudinal qualitative datasets were collected in 2021-2023 from ten non-genetics physicians working in hospitals in Victoria, Australia. Reflexive thematic analysis was used to characterise participants' perceptions of, and workplace interactions with, genomic experts. Deductive content analysis was then applied to sort and synthesise participants' relationships with genomics experts. Designated the 'Genomics Friend', these individuals are trained in genetics or recognised as same-specialty genomic champions and perceived as trusted and accessible sources of genomic expertise. Participants who had a Genomics Friend leveraged their established relationship on an ad hoc basis to address identified knowledge gaps. Sorting participants into the Genomics Friend Relationship Matrix demonstrated how having a Genomics Friend enhanced genomic workplace learning and practice for physicians across different career stages and specialties. These findings offer insights into how intra- and inter-disciplinary interactions and collegial relationships provide professional development opportunities through workplace learning. Moreover, we consider how genomic expert 'friends' could support implementation efforts by facilitating the health workforce to learn, adopt and practise genomics.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insertion or deletion variants in TAF15 exon 15 are genetic factors impacting the prognosis of amyotrophic lateral sclerosis in a Japanese cohort.","authors":"Yuya Hatano, Tomohiko Ishihara, Mari Tada, Yutong Li, Sachiko Hirokawa, Masahiro Uemura, Shoichiro Ando, Akio Yokoseki, Akiyoshi Kakita, Osamu Onodera","doi":"10.1038/s41431-026-02249-w","DOIUrl":"https://doi.org/10.1038/s41431-026-02249-w","url":null,"abstract":"<p><p>The influence of genetic factors on the prognosis of amyotrophic lateral sclerosis (ALS) has attracted considerable attention, with numerous studies exploring this relationship in clinically diagnosed patients. The present study attempted to clarify the precise impact of genetic factors on prognosis in patients with pathologically confirmed sporadic ALS. We conducted exome analysis on 137 consecutively autopsied patients with sporadic ALS exhibiting TDP-43 pathology, screening for non-synonymous or splice-site rare variants (RVs) in ALS-related genes. The impact of these variants on ALS prognosis was subsequently assessed. The exome analysis identified 31 RVs in 27 of the 137 patients, including TAF15 exon 15 insertion/deletion mutations (TAF15-15 indels) in 9 patients. Patients harboring RVs had significantly shorter survival times (median 18.0 months) than those without RVs (28.5 months), as determined by log-rank test (p = 0.02). Notably, the 9 cases with TAF15-15 indels demonstrated a significantly poorer outcome (15.0 months, p = 3e-06). Lattice Simulation of Sticker-Spacer Interactions (LASSI) simulations revealed stronger negative sticker-sticker interactions, and a tendency toward lower saturation concentration and higher dense-phase concentration in TAF15-15 indel proteins, suggesting enhanced condensation. The present analysis of pathologically diagnosed ALS patients has yielded genetic factors that could potentially aid more accurate diagnosis and prognostication. The frequent identification of TAF15-15 indels among ALS cases, and their association with significantly poorer outcome, suggests that this type of mutation could be prognostically significant in ALS. Furthermore, the mechanism by which TAF15-15 indels influence the course of ALS could be a promising target for future treatments.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanded carrier screening in China: a focused narrative review and conceptual implementation framework.","authors":"Liling Liu, Honglian Wu, Ming Zhang, Yinghui Ye, Dong Yu, Ming Qi, Xutao Hong","doi":"10.1038/s41431-026-02252-1","DOIUrl":"https://doi.org/10.1038/s41431-026-02252-1","url":null,"abstract":"<p><p>Expanded carrier screening (ECS) is increasingly used in China, but implementation remains heterogeneous across regions, laboratories, and reproductive-care settings. This focused narrative review synthesizes Chinese evidence on population variation, panel design, analytical methods, variant interpretation, couple-level reproductive risk, and health-system delivery. The review was informed by a reproducible PubMed search through 29 July 2026, supplemented by targeted identification of Chinese empirical studies and professional guidance. Chinese studies demonstrate substantial variation in carrier frequencies and screening yield across populations, while reported carrier and at-risk couple (ARC) rates are strongly influenced by panel composition, analytical methods, and variant-reporting criteria, particularly the inclusion of low-penetrance variants. Technical limitations at structurally complex loci and uneven access to genetic counseling and laboratory resources further affect implementation. On this basis, we propose a review-derived conceptual framework centered on universal minimum access, core screening principles, population-informed content adaptation, separation of variant-level classification from couple-level reproductive-risk assessment, and health-system support. Regional epidemiology and founder variants may inform panel content but should not determine screening eligibility. The framework also emphasizes partner testing, counseling and referral pathways, quality assurance, reimbursement, and measurable implementation outcomes. It is intended to organize current evidence and support future consensus development rather than function as a validated clinical guideline. Prospective multicenter evaluation, stakeholder consensus, and China-specific health-economic analyses are needed before national practice recommendations can be established.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manufactured gametes and the principle of genetic caution.","authors":"Joona Räsänen, Adrian Villalba, Julian Savulescu","doi":"10.1038/s41431-026-02254-z","DOIUrl":"https://doi.org/10.1038/s41431-026-02254-z","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reanalysis of genomic data doubles the diagnostic yield for Welsh patients recruited to the UK 100,000 Genomes Project.","authors":"Jana Jezkova, Martin A McClatchey, Sophie Shaw, Rhys Vaughan, Joseph Halstead, Iris Egner, Sharon D Whatley, Arveen Kamath, Oliver Murch, Vinod Varghese, Rachel Irving, Jennifer F Gardner, Ayesha Ahmed, Ian Tully, Vani Jain, Mark T Rogers, Francis H Sansbury, Angus J Clarke, Caroline Pottinger, Maribel Verdesoto Rodriguez, Johann Te Water Naudé, Aimee Bettridge, Alexandra C Martin-Geary, Nils Wagner, Julien Gagneur, Marcela Votruba, David J Bunyan, Kevin Ashelford, Peter Giles, Hywel J Williams, Sian Morgan, Julian R Sampson, Andrew E Fry","doi":"10.1038/s41431-026-02234-3","DOIUrl":"https://doi.org/10.1038/s41431-026-02234-3","url":null,"abstract":"<p><p>The 100,000 Genomes Project (100KGP) undertook genome sequencing of patients with rare diseases and cancer to study the role that genes play in disease, and to integrate genomics into UK healthcare. To contribute to 100KGP, the Wales Genomic Medicine Centre (a partnership between the NHS All Wales Medical Genomics Service (AWMGS), Cardiff University and Genomics England) recruited 438 individuals from 154 families that had been subject to pre-genomic genetic testing without reaching a diagnosis. The majority of probands (64%, 98/154) had neurological or neurodevelopmental phenotypes. Genome sequencing, variant calling, gene-based filtering and variant prioritisation were performed by Genomics England. AWMGS undertook clinical interpretation, validation and reporting of variants. Initial diagnostic yield was 20.8% (32/154) with variants of uncertain significance (VUS) reported for 11 more families. Most of the initial findings (83.7%, 36/43) could have been detected by clinical exome sequencing which was standard of care in Wales at the time. Reanalysis of the 100KGP Wales data using updated variant prioritisation tools, expanded gene lists, re-phenotyping and segregation studies, has increased diagnostic yield to 42.2% (65/154) (an improvement of 103%). RNA analysis was used to clarify the clinical significance of VUS in COQ4, ENPP1, GATAD2B, NCAPD2, and THOC2. These findings demonstrate the clinical utility of genome sequencing, RNA analysis, and periodic reanalysis of genomic data.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interdisciplinary management and genetic evaluation of pediatric cancer predisposition syndromes: a retrospective cohort study.","authors":"Nicola Dikow, Anna Lisa Nitschke, Steffen Hirsch, Eva Roth, Laura Orec, Tom Fischer, Daniela Choukair, Kerstin Grund, Peggy Lüttich, Christian Sutter, Katrin Hinderhofer, Heiko Brennenstuhl, Cornelis M van Tilburg, Olaf Witt, Markus Großmüller, Alexander Fichtner, Katrin Willig, David T W Jones, Maja Hempel, Andreas E Kulozik, Ute Bartels, Till Milde, Christian P Schaaf, Stefan M Pfister, Joachim Kunz, Kristian W Pajtler","doi":"10.1038/s41431-026-02244-1","DOIUrl":"https://doi.org/10.1038/s41431-026-02244-1","url":null,"abstract":"<p><p>Comprehensive knowledge of cancer predisposition syndromes (CPS) is essential for the implementation of surveillance programs with proven clinical benefit. An interdisciplinary expert panel was established at our center to facilitate early identification of children with suspected CPS. This retrospective cohort study assessed the diagnostic yield and clinical impact of this consultation model. A total of 144 pediatric patients were evaluated. Clinical characteristics, family histories, and molecular diagnostic results were systematically retrieved from medical records. Of the 144 individuals, 99 presented with clinical features suggestive of CPS, of whom 53 had cancer. Clinically asymptomatic children (45/144) were referred due to positive family history. Prior to consultation, 34 of 99 symptomatic patients had been diagnosed with CPS. Among those symptomatic and undiagnosed undergoing molecular genetic testing, a disease-causing variant was identified in CPS genes in 46% (23/50). Predictive testing in asymptomatic children revealed the familial pathogenic variant in 43.8% (14/32). Nearly all patients with confirmed CPS 93,4% (71/76) received surveillance recommendations. The interdisciplinary CPS consultation model contributes to identifying hereditary cancer predisposition in pediatric patients and families. This expert-led approach emphasizes the importance of personalized surveillance strategies for rare CPS entities and provides a scalable foundation for systematic CPS assessment and development of standardized, evidence-based surveillance protocols in pediatric oncology.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}