European Journal of Human Genetics最新文献

{"title":"Predisposition to prostate cancer and clinical implications in a real-life cohort","authors":"Julie Chartier, Albain Chansavang, Anne Jouinot, Nadim Hamzaoui, Arunya Srikaran, Diane Molière, Olivier Huillard, Constance Thibault, Manuela Tiako, Mathilde Sibony, Pierre Laurent-Puig, Eric Pasmant, Camille Tlemsani","doi":"10.1038/s41431-025-01859-0","DOIUrl":"10.1038/s41431-025-01859-0","url":null,"abstract":"Genetic predisposition is identified in 5–10% of prostate cancer patients. Although genetic testing is more frequently proposed, international recommendations are lacking. This study evaluates the impact of germline analysis on management of prostate cancer patients. Retrospective descriptive data were collected from prostate cancer patients who attended oncogenetic counselling between 2018 and 2021. Data included clinical and tumoral characteristics, and genomic analysis. Comparative analysis was performed between patients with germline pathogenic variants (PVs) and non-carriers using non-parametric tests. Fourteen out of the 168 patients (8.3%) had a PV, primarily in DNA repair genes (N = 13/14), including BRCA1/2 (N = 5). Twenty-five patients (14.9%) had variants of undetermined significance. Patients with PVs were more likely to have synchronous metastatic extension (79% vs 43%, p = 0.02) and a Gleason score ≥8 (82% vs 53%, p = 0.11). Significant enrichment of ATM PVs compared to a healthy control cohort was observed with an odds ratio of 32.5 [15.8–67.0] (p < 0.05). Three of five patients with BRCA1/2 PVs received DNA repair-targeted treatment. This cohort provides insights into the impact of oncogenetic counselling on prostate cancer patients’ management. It highlights the need to refine referral criteria based on disease stage and Gleason score and to further investigate ATM PVs. The data also underscore the importance of developing a care pathway with clear criteria for germline and/or somatic analysis to improve theranostic outcomes.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 9","pages":"1163-1172"},"PeriodicalIF":4.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976450","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":"What’s new in EJHG in May 2025?","authors":"Alisdair McNeill","doi":"10.1038/s41431-025-01857-2","DOIUrl":"10.1038/s41431-025-01857-2","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 5","pages":"559-560"},"PeriodicalIF":3.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41431-025-01857-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897277","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":"GJA8-associated developmental eye disorders: a new multicentre study highlights mutational hotspots and genotype-phenotype correlations","authors":"Solomon S. Merepa, Linda M. Reis, Alejandra Damián, Tanya Bardakjian, Adele Schneider, María Jose Trujillo-Tiebas, Carmen Ayuso, Laura Cortázar Galarza, Raquel Saez Villaverde, Nelmar Valentina Ortiz-Cabrera, Dorine A. Bax, Richard Holt, Fabiola Ceroni, Patrick Edery, Maude Grelet, Florence Riccardi, Lauriane Maillard, Deborah Costakos, Julie Plaisancié, Nicolas Chassaing, Marta Corton, Elena V. Semina, Nicola K. Ragge","doi":"10.1038/s41431-025-01843-8","DOIUrl":"10.1038/s41431-025-01843-8","url":null,"abstract":"Variants in gap junction protein alpha 8 (GJA8), the gene encoding connexin 50 (Cx50), are primarily associated with developmental cataract, although some are associated with severe structural eye anomalies, such as aphakia (absent lens), microphthalmia (small eyes), and sclerocornea. To further define the relationship of GJA8 variants to ocular developmental disorders, we screened four large international cohorts with structural eye anomalies, including anophthalmia, microphthalmia, and coloboma (AMC) or cataracts. We identified 15 new families carrying 14 different heterozygous GJA8 variants (12 missense variants and two 1q21 microdeletions). The missense variants comprised 10 previously reported alterations in cases with eye anomalies [p.(Gly22Ser), p.(Val44Met), p.(Asp67Gly), p.(Arg76Cys), p.(Pro88Leu), p.(Gly94Glu), p.(Gly94Arg), p.(His98Arg), p.(Pro189Ser), and p.(Arg198Trp)] and two not yet linked with disease [p.(Thr39Met) and p.(Tyr66Asp)]. Their associated phenotypes ranged from isolated cataracts to a combination of microphthalmia and cataract with/without sclerocornea. Our study confirms GJA8 variants as an important source of genetic diagnoses for families with structural eye anomalies in addition to cataract and highlights specific mutational hotspots. Furthermore, we confirm an important genotype-phenotype correlation between sclerocornea and the p.(Gly94Arg) variant, and detail intra- and inter-familial phenotypic variability, which is important for clinical assessment and genetic counselling.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 7","pages":"860-869"},"PeriodicalIF":3.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41431-025-01843-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974006","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":"Comment on Building a hereditary cancer program in Colombia: analysis of germline pathogenic and likely pathogenic variants spectrum in a high-risk cohort","authors":"Mev Dominguez-Valentin","doi":"10.1038/s41431-025-01853-6","DOIUrl":"10.1038/s41431-025-01853-6","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 7","pages":"829-830"},"PeriodicalIF":3.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41431-025-01853-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997445","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":"More of the same? Israel's expanded carrier screening for cystic fibrosis.","authors":"Tamar Nov-Klaiman, Ruth Horn, Aviad Raz","doi":"10.1038/s41431-025-01851-8","DOIUrl":"https://doi.org/10.1038/s41431-025-01851-8","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973848","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":"The Spanish Polygenic Score reference distribution: a resource for personalized medicine.","authors":"Rosario Carmona, Gema Roldán, Jose L Fernández-Rueda, Arcadi Navarro, María Peña-Chilet, Joaquín Dopazo, Daniel López-López","doi":"10.1038/s41431-025-01850-9","DOIUrl":"https://doi.org/10.1038/s41431-025-01850-9","url":null,"abstract":"<p><p>Here we present the Polygenic Score (PGS) distributions for 3124 common diseases and quantitative traits observed in the Spanish population. To achieve so, the genomes and exomes of 2190 unrelated individuals of Spanish ancestry were used. The analysis covered a wide range of diseases and traits, including both complex disorders, such as various types of cancer, and disorders associated with the digestive, cardiovascular, neuronal, and immune systems, as well as quantitative traits like hematological and anthropometric measurements. The resulting PGS distributions provide valuable insights into the genetic architecture of the Spanish population, offering a comprehensive framework for investigating disease susceptibility and potential risk factors in this specific population. The study has also explored potential relationships between diseases and traits based on PGS pairwise correlations, revealing significant correlations that warrant further investigation. These findings have contributed to increase our understanding of the genetic basis of human traits and have implications for personalized medicine and public health interventions in the Spanish population. In addition, for the sake of reproducibility, we provide a data processing pipeline, enabling the computation of PGS for external genomes and exomes. The pipeline, accessible on GitHub, supports parallel tasks on various computing platforms and contributes to the standardization of PGS comparisons globally. Lastly, a user-friendly web interface facilitates the exploration of PGS reference distributions, featuring a detailed table, distribution plots, and filtering options. This interface enhances accessibility for researchers and clinicians, fostering informed decision-making based on population-specific PGS distributions. The PGS reference distributions can be explored at the SpPGS Atlas repository through the web interface: https://csvs.clinbioinfosspa.es/?tab=pgs .</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984593","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":"Endure or perish with use of artificial intelligence in clinical genetics settings","authors":"Partha Pratim Ray","doi":"10.1038/s41431-025-01852-7","DOIUrl":"10.1038/s41431-025-01852-7","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 7","pages":"826-828"},"PeriodicalIF":3.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997375","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":"Vascular Ehlers Danlos Syndrome and Chromosome 2q32 Microdeletion Syndrome","authors":"Claire E. Green,&nbsp;Shadi Albaba,&nbsp;Glenda J. Sobey,&nbsp;Jessica M. Bowen,&nbsp;Deirdre E. Donnelly,&nbsp;Marina Colombi,&nbsp;Marco Ritelli,&nbsp;Athalie Melville,&nbsp;Neeti Ghali,&nbsp;Fleur S. van Dijk,&nbsp;Emma Hobson,&nbsp;Jessica A. Radley,&nbsp;Esther Kinning,&nbsp;Abhijit Dixit,&nbsp;Simon McCullough,&nbsp;Duncan Baker,&nbsp;Diana S. Johnson","doi":"10.1038/s41431-025-01849-2","DOIUrl":"10.1038/s41431-025-01849-2","url":null,"abstract":"Interstitial deletions of 2q32 are typically identified after investigation for developmental delay. Two genes associated with Ehlers Danlos Syndrome (EDS); COL3A1 and COL5A2 associated with vascular EDS and classical EDS respectively, may be incorporated in the region. Although many reports of 2q32 microdeletion patients exist, there is little mention of these genes with only a few reports highlighting features potentially linked with EDS. This paper reviews the literature and presents eleven new patients with 2q32 deletions that encompass COL3A1 and COL5A2. We describe their clinical manifestations with a particular focus on the EDS phenotype. Most patients showed some minor features of vascular EDS and one patient had vessel rupture at a young age. Analysis of skin biopsy findings from two patients showed features consistent with vascular EDS but no features of classical EDS. The findings from this cohort provide additional evidence that haploinsufficiency is an important disease mechanism in COL3A1 but not COL5A2. We highlight the importance of pre-test counselling for incidental findings from broad genetic testing and appropriate post-test counselling to ensure follow up is provided to manage the implications of a vascular EDS diagnosis.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 10","pages":"1309-1315"},"PeriodicalIF":4.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989915","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":"Empowering human research ethics committees to review genomics applications: evaluating the utility of a custom online education resource","authors":"Ella McGahan,&nbsp;Jennifer Berkman,&nbsp;David Milne,&nbsp;Bronwyn Terrill,&nbsp;Russell Gear,&nbsp;Susan Gardiner,&nbsp;Lisa Eckstein,&nbsp;Dianne Nicol,&nbsp;Natalie Taylor,&nbsp;Ingrid Winship,&nbsp;Rebekah McWhirter,&nbsp;Amy Nisselle,&nbsp;Jason Lodge,&nbsp;Aideen McInerney-Leo","doi":"10.1038/s41431-025-01846-5","DOIUrl":"10.1038/s41431-025-01846-5","url":null,"abstract":"Complex genomic technologies are increasingly utilised in research. However, human research ethics committee (HREC) members lack confidence reviewing genomics applications. This study developed and evaluated the acceptability and utility of an online educational resource on genomics and the ethical considerations for HREC members. Resource development and evaluation was theoretically informed. Qualitative semi-structured interviews with HREC members and subject experts were transcribed and deductively analysed. Participants (n = 29) found the content to be comprehensive, appropriately pitched, and optimal in quantity. Most reported the resource was easy to access and intuitive to navigate. HREC members reported improved confidence in reviewing genomics ethics applications and intentions to re-access as needed. Most (n = 28/29) would recommend to other HREC members, and some volunteered that they would recommend to researchers. Suggested navigation improvements included a progress bar, active learning elements, and a more clearly visible menu. Content suggestions included more detail on data storage/management and considerations when engaging diverse communities. This is the first study to develop and evaluate a genomic educational resource tailored to ethics committees. Following refinement and quantitative evaluation, it is hoped that this resource will increase HREC member confidence in reviewing genomics ethics applications and the quality of researchers’ submissions.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 7","pages":"945-955"},"PeriodicalIF":3.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41431-025-01846-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964913","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":"Cost-effectiveness of population-based expanded reproductive carrier screening for genetic diseases in Australia: a microsimulation analysis","authors":"Deborah Schofield,&nbsp;Evelyn Lee,&nbsp;Jayamala Parmar,&nbsp;Adriana Castelo Taboada,&nbsp;Matthew Hobbs,&nbsp;Nigel Laing,&nbsp;Rupendra Shrestha","doi":"10.1038/s41431-025-01835-8","DOIUrl":"10.1038/s41431-025-01835-8","url":null,"abstract":"Using the Australian Census survey 2021 as base population, a microsimulation model, PreconMOD was developed to evaluate the cost-effectiveness of population-based expanded reproductive carrier screening (RCS) for 569 recessive conditions from the health service and societal perspectives. The model simulated the effect of expanded RCS including the downstream interventions for at-risk couples on cost and outcomes. The comparators were (i) no population screening (ii) limited screening for cystic fibrosis, spinal muscular atrophy, and fragile X syndrome and (iii) a 300 conditions screening panel. Averted affected births and health service cost with expanded RCS were projected to year 2061. At a 50% uptake, our model predicts that expanded RCS is cost saving (i.e., higher quality-adjusted life-years and lower costs) compared with other screening strategies in the model from the health service and societal perspectives. The number of affected births averted in a single cohort would increase from 84 [95% confidence interval (CI) 60–116] with limited screening to 2067 (95%CI 1808–2376) with expanded RCS. Expanded RCS was cost-saving compared to the 300-conditions screening panel. Indirect cost accounted for about one-third of the total costs associated with recessive disorders. Our model predicts that the direct treatment cost associated with current limited 3 genes screening would increase by 20% each year to A$73.4 billion to the health system by 2061. Our findings contribute insights on the cost burden of genetic diseases and the economic benefits of expanded RCS to better informed resource allocation decisions.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 9","pages":"1180-1187"},"PeriodicalIF":4.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01835-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969741","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}