European Journal of Human Genetics最新文献

{"title":"Genomic newborn screening: a scoping review of the field's evolution and associated ethical, legal, and social implications.","authors":"Gemma L Brown, Loren Walker, Mutiat A Afolabi, Paul A Bain, Ana Bonilha, Bimal P Chaudhari, John Christodoulou, Ziyi Dai, Jan M Friedman, Amy Gaviglio, Robert C Green, Subhashini Jagu, Bartha M Knoppers, Ainsley J Newson, Zornitza Stark, Danya F Vears, Aliza Wilson, Yvonne Bombard, Anna C F Lewis","doi":"10.1038/s41431-026-02108-8","DOIUrl":"https://doi.org/10.1038/s41431-026-02108-8","url":null,"abstract":"<p><p>The integration of genomic sequencing into newborn screening (genomic newborn screening; gNBS) has the potential to identify more presymptomatic babies who could benefit from early intervention compared to traditional universal newborn screening (NBS). Realizing these benefits requires careful navigation of ethical, legal, and social implications (ELSI) to minimize harms, promote equity, and maintain trust in NBS programs. The primary objective of this scoping review is to synthesize the ELSI discussed in the gNBS literature, to support implementation and identify knowledge gaps. A secondary objective is to characterize the landscape and contours of the gNBS field. This review, conducted in July 2025, includes academic literature addressing genomic sequencing as a first‑line NBS screen. ELSI were identified within each publication, and these informed the development of a set of decision points with ELSI dimensions within gNBS. A total of 485 publications met inclusion criteria, with the first published in 1987. The volume of publications increased over time, with growing proportions of empirical studies and work associated with gNBS projects, alongside a decreasing proportion of publications from North America. In total, 3781 ELSI considerations were charted using AI-assisted methods, relevant to 59 decision points organized into nine areas. Current scholarship is concentrated on early implementation questions, while long‑term operational needs-such as data stewardship, clinical follow‑up, and sustainable governance-remain underexplored. These gaps, together with limited contributions from many regions due to a multitude of factors, highlight the need for more diverse, empirically grounded, and forward‑looking research to support responsible decisions around gNBS.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856013","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":"Facing suffering honestly: On severity, utility, and the public good in reproductive genetic carrier screening.","authors":"Hafez Ismaili M'hamdi, Sanne van der Hout, Angus Clark, Guido de Wert","doi":"10.1038/s41431-026-02123-9","DOIUrl":"https://doi.org/10.1038/s41431-026-02123-9","url":null,"abstract":"<p><p>Reproductive genetic carrier screening (RGCS) raises the question of which conditions should be included. Severity has long been the guiding criterion: conditions causing serious suffering, justify offering reproductive options. Some propose replacing severity with utility, defined as the usefulness of information for reproductive decision-making. Proponents of this approach claim that utility aligns more directly with RGCS's aim of supporting informed choice while avoiding stigmatizing judgments about genetic conditions. This article challenges that proposal. First, utility depends on severity: contextual factors such as preimplantation genetic testing become relevant only once a condition is judged sufficiently severe. Second, while severity retains some clinical anchors such as prognosis, functional limitations, treatment burden, utility dissolves into subjective preferences, making it ill-suited for guiding population-level policy. Third, collective recognition of severity provides prospective parents with a moral frame of reference that eases the heavy responsibility of reproductive decisions. Fourth, avoiding severity judgments in the name of respect risks both invalidating the suffering of affected individuals and bypassing the democratic deliberation essential to public healthcare policy. We argue that value judgments in RGCS are inevitable and necessary. Severity, though imperfect, provides the shared normative anchor needed for publicly funded programs. Facing suffering honestly, acknowledging severity while respecting those who live with severe conditions, is the foundation of a compassionate and democratic RGCS policy.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835134","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":"Genomic newborn screening: data retention for research and clinical reuse.","authors":"Anna C F Lewis, Aaron J Goldenberg, Bartha M Knoppers","doi":"10.1038/s41431-026-02120-y","DOIUrl":"https://doi.org/10.1038/s41431-026-02120-y","url":null,"abstract":"<p><p>The integration of genomic sequencing into public health newborn screening (NBS), gNBS, could identify far more children that would meet screening guidelines than existing biochemical NBS. The retention of genomic data from gNBS could have huge benefits for research and could also enable potential clinical reuse. Many different ethical frameworks can support not seeking parental permission for traditional NBS, and indeed, most programs around the world do not do so, and are either mandatory or allow for an opt-out. Many NBS programs retain the underlying sample for anonymized or pseudonymized/coded research. This is proving to be a controversial aspect of NBS. While the appropriate consent regime(s) for the screening aims for gNBS remain unclear, we put forward arguments for the appropriate consent regimes for the retention and use of genomic data in gNBS. We review the different ethical frameworks that justify screening on the one hand, and further storage and uses of the data on the other. We argue that parental permission via an informed choice should be sought for genomic data retention for research purposes, that individual genomic data may be retained by the program for QA/QI purposes (but only for long enough to permit these purposes), and that no parental permission is needed to update aggregated genomic databases (e.g., allele frequencies). For clinical recontact, the appropriate consent regime for retaining genomic data will depend on the jurisdiction, but parents should be very thoroughly educated on the prospect of re-contact if this is planned.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835434","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":"Harmonizing the genetic counselor profession in Europe.","authors":"Rebecka Pestoff, Christophe Cordier, Donna Darmanin, Katrin Õunap, Christi J van Asperen","doi":"10.1038/s41431-026-02097-8","DOIUrl":"https://doi.org/10.1038/s41431-026-02097-8","url":null,"abstract":"<p><p>Genetics in medicine is rapidly becoming integral to European healthcare, yet access to high-quality genetic counseling remains inconsistent. Genetic counseling empowers patients to make informed decisions about genetic testing, improves clinical management, and mitigates psychosocial harm. Despite growing demand, the genetic counselor profession lacks legal recognition, standardized education, and harmonized regulation across European Union (EU) Member States. Current fragmentation, which is evident in separate national laws and variable practices, poses systemic risks, including inequitable care and credentialing barriers. This paper argues that harmonization is essential to ensure ethical, safe, and effective genetic services. We recommend EU-wide legal recognition of genetic counselors, standardized education through EBMG-accredited programs, and investment in workforce development and education. Coordinated action can safeguard individuals' rights, support professional mobility, and enable responsible integration of genomics into healthcare.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835377","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":"Long-term survival without high cancer risk in a cohort of 24 patients with Apert syndrome.","authors":"Benjamin J Cairns, Dominique M Davidson, Sarah F Smithson, Andrew O M Wilkie","doi":"10.1038/s41431-026-02122-w","DOIUrl":"https://doi.org/10.1038/s41431-026-02122-w","url":null,"abstract":"<p><p>The classification of congenital malformations has been transformed over recent decades by advances in genetic analysis, so that the natural history of many disorders during childhood is well described. However, implications for adult prognosis and survival are often poorly documented. In Apert syndrome, caused by heterozygous germline mutations in the fibroblast growth factor receptor type 2 gene (FGFR2), the question of prognosis is particularly pertinent because FGFR2 is a known cancer driver gene (oncogene) and the identical mutations, when arising somatically, are enriched in specific tumours, notably endometrial carcinoma. We exploited a unique resource provided by a series of 24 UK patients described by Dr Eric Blank in 1960, and used tracing of cancer events and deaths through the National Health Service Central Register to determine the long-term outcome of these individuals until 2013, a period spanning 53 years. Twelve individuals (50%) were still alive and without any cancer registration, at the end of the study; of the remainder, two could not be traced and ten were known to have died, with four deaths related to malignancies. We conclude that Apert syndrome is not, in many affected individuals, associated either with substantial shortening of lifespan, or with a high risk of developing particular types of cancer. Explanation of the lack of strong cancer predisposition, despite the oncogenic nature of the FGFR2 mutations, may lie in the different signalling relationship that a mutant cell has with its neighbours when the mutation is present constitutionally, compared to occurrence as a somatic change.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835416","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":"Advancing training on genetic therapies: a multi-specialty survey highlighting the role of medical geneticists.","authors":"R Díaz Jiménez, Y Trakadis","doi":"10.1038/s41431-026-02102-0","DOIUrl":"https://doi.org/10.1038/s41431-026-02102-0","url":null,"abstract":"<p><p>This cross-sectional online survey study explores the landscape of medical training on genetic therapies, assessing the experience, expectations and attitudes of medical geneticists, other specialists, and medical trainees in Canada and USA. Among the 315 participants, only 17% reported being \"very familiar\" with genetic therapies, and 70% expressed dissatisfaction with current training in this area. Across all groups, there was a consistently low level of satisfaction with existing training on genetic therapies, coupled with a strong consensus that this topic should be better integrated into medical programs. Physicians with specialization in genetics reported the highest familiarity and the most experience in teaching about genetic therapies, covering a broader range of topics than other specialties. All specialties acknowledged the pivotal role of medical geneticists in advancing education on genetic therapies. Instead of each specialty designing their own fellowship programs independently, there was a clear preference to do so in collaboration with medical geneticists. Furthermore, most respondents advocated for the introduction of genetic therapy education earlier in medical training, during medical school and residency programs. Our study highlights a clear and pressing need for comprehensive, stage-specific education reform about genetic therapies. Medical geneticists are uniquely positioned to lead and support these educational efforts, ensuring the successful adoption of advanced genetic therapies in patient care.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835105","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":"Abstracts of the 8th International Workshop on the History of Human Genetics: The History of Eugenics, Evolution of Techniques in Human Genetics and Women in the History of Human Genetics.","authors":"","doi":"10.1038/s41431-026-02092-z","DOIUrl":"https://doi.org/10.1038/s41431-026-02092-z","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835121","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":"Genomic inversion at 6p22.3 supports ID4 dysregulation as the pathogenic mechanism of Mesomelic dysplasia Savarirayan-type.","authors":"Elsa Lucas-Castro, Rosario Ramos-Mejía, Víctor Sánchez-Gaya, Álvaro Rada-Iglesias, Silvia Caíno, Virginia Fano, Karen E Heath","doi":"10.1038/s41431-026-02124-8","DOIUrl":"https://doi.org/10.1038/s41431-026-02124-8","url":null,"abstract":"<p><p>Mesomelic dysplasia Savarirayan-type or ID4-related (MDST) is an ultra-rare skeletal dysplasia caused by chromosome 6p22.3 microdeletions. To date, only four cases have been reported. Here, we report a fifth case, a 9 year-old female with severe mesomelic lower limb shortening and characteristic radiographic findings, highly resembling those identified in previous MDST patients. No deletion was identified by array. However, whole genome sequencing (WGS) revealed a de novo inversion at 6p22.3. As hypothesized for deletions detected in this disorder we predict that the structural variant disrupts several topologically associated domains (TADs) in the region and is likely to place ID4 in closer proximity to more telomerically located limb enhancers, which could result in enhancer adoption and potentially lead to ID4 limb misexpression. Thus, this case broadens the genetic spectrum in MDST and provides further support to the role of ID4 dysregulation as the main underlying molecular mechanism of this ultra-rare skeletal disorder.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812631","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":"Prevalence of deleterious variants in cardiomyopathy genes in early-onset atrial fibrillation.","authors":"Oliver Bundgaard Vad, Quim Bech Vilaseca, Astrid Filt Beyer, Christian Paludan-Müller, Laura Andreasen, Jesper Hastrup Svendsen, Pia Rengtved Lundegaard","doi":"10.1038/s41431-026-02119-5","DOIUrl":"10.1038/s41431-026-02119-5","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke, heart failure, and death. Recent studies suggest that early-onset AF increases the risk of developing heart failure and dilated cardiomyopathy. This study aimed to identify genetic variants in a large set of 34 cardiomyopathy genes among early-onset AF individuals. We conducted targeted sequencing of cardiomyopathy-associated genes in 478 individuals from a Danish cohort with early AF onset. Additionally, we analyzed whole exome sequencing data from 375,869 individuals from the UK Biobank, including 29,267 individuals with AF. Of the Danish individuals with early-onset AF, 8.8% carried pathogenic or likely pathogenic (P/LP) variants in cardiomyopathy-associated genes. The prevalence of rare P/LP variants in the UK Biobank analysis ranged from 3.85% in the group with early AF onset to 1.03% in the group without AF diagnosis. Results were largely consistent when excluding individuals with no prior cardiomyopathy or heart failure diagnosis. This suggests that genetic testing for cardiomyopathy could be relevant in selected individuals with early AF diagnosis.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812701","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":"SLC52A3-related Brown-Vialetto-Van Laere syndrome: a large cohort from the Arabian Peninsula.","authors":"Bushra Al Shamsi, Momen Al Momen, Farah Al Kindy, Sami Al-Kalbani, Amna Al-Futaisi, Maha Al-Awadi, Yasir Al Abri, Khalid Al-Thihli","doi":"10.1038/s41431-026-02106-w","DOIUrl":"https://doi.org/10.1038/s41431-026-02106-w","url":null,"abstract":"<p><p>SLC52A3-related Brown-Vialetto-Van Laere syndrome (BVVL) is a rare neurodegenerative disorder characterized by progressive motor and sensory impairment, with high mortality rate if left untreated. We hereby report the largest cohort with SLC52A3-related BVVL from the Arabian Peninsula. A total of 23 patients, 16 females and 7 males, with genetically confirmed BVVL diagnosis at two tertiary centers from the region were retrospectively reviewed. Most patients were clinically ascertained (13/23), while 10 patients were diagnosed pre-symptomatically. 20 patients were homozygous for SLC52A3: c.634C>T (p.Arg212Cys) variant and 3 patients were homozygous for SLC52A3: c.1325_1326del. Facial diplegia was the commonest clinical feature (12/13), while moderate to severe hearing loss and dysarthria were seen in (10/13) patients. Symptomatic patients were treated with riboflavin doses ranging between 15 and 100 mg/Kg/day, with a median of 26 mg/Kg/day. Pre-symptomatic patients were treated with doses lower than that (as low as 5 mg/Kg/day). Patients were followed for 6 months to 12 years, with a median of 4 years. Most patients have shown significant or near-total recovery with residual symptoms (11/13), while 9/10 patients diagnosed pre-symptomatically remained symptom-free, and 2 symptomatic patients showed complete resolution of symptoms. The study emphasizes the significant interfamilial and intrafamilial variability of BVVL, and it stresses the impact of early treatment with riboflavin in the prevention of morbidity and mortality associated with this condition. The study also provides the longest cumulative follow-up of pre-symptomatically treated patients reported to date, providing preliminary evidence for the role of riboflavin in the prevention of morbidities associated with this condition.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766413","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}