European Journal of Human Genetics最新文献

{"title":"Vertical inheritance and unique differential phenotypes of reciprocal recombinant chromosome 18 within a multi-generation family.","authors":"Ting Wen, Gulsen Akay, Janice Palumbos, Betsy Ostrander, Denise I Quigley, Allen N Lamb, Erica F Andersen, Bo Hong, David Viskochil","doi":"10.1038/s41431-025-01878-x","DOIUrl":"https://doi.org/10.1038/s41431-025-01878-x","url":null,"abstract":"<p><p>Carriers of balanced pericentric inversions are at risk for producing unbalanced gametes because of meiotic recombination resulting in de novo deletion and duplication of distal chromosome ends. Recombinant chromosomes generally lead to significant imbalances resulting in anomalous clinical phenotypes in offspring, hence they are typically not inherited. Therefore, the vertical transmission of recombinant chromosomes is a clinically rare event. Using genomic microarray and karyotyping, we describe inheritance of recombinant chromosomes in a three-generation family with the grandmother carrying a mosaic pericentric inversion of chromosome 18. Three children inherited the balanced inversion and one child with a mild phenotype inherited a de novo recombinant chromosome 18. In the third generation, a newborn with a variant of holoprosencephaly inherited an unmodified recombinant chromosome from her mother. Despite having the same karyotype predicting loss of the TGIF1 gene from the 18p terminus, the mother exhibits a relatively unaffected phenotype. The cousin of the child with holoprosencephaly carries the reciprocal recombinant chromosome 18 with a much milder phenotype. We verified the cytogenetic mechanism and corresponding clinical phenotypes in affected individuals and illustrated possible recombinant chromosome consequences of the inversion of chromosome 18 in this three-generation family.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590795","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":"Interrupted CTG repeats in the 37-43 units size range in the 3'UTR of DMPK are common alleles.","authors":"Hilde Swinkels, Maike Leferink, Maartje Pennings, Bart van der Sanden, Christian Gilissen, Jordi Corominas Galbany, Erik-Jan Kamsteeg","doi":"10.1038/s41431-025-01907-9","DOIUrl":"10.1038/s41431-025-01907-9","url":null,"abstract":"<p><p>The size of non-pathogenic CTG repeats in the 3'UTR of the DMPK gene varies from 5-35, whereas repeats over 50 units are pathogenic. The Intermediate repeats of 36-50 are considered 'premutation', as they are present in individuals unaffected by myotonic dystrophy, but are prone to further enlargement into the pathogenic range upon transmission to offspring. In this study, we showed that CCGCTG interrupted intermediate repeats, in the repeat size of 37-43 units, have been detected in multiple families with a history of myotonic dystrophy. However, segregation and microsatellite marker analysis of these interrupted intermediate alleles revealed that these alleles are not the same alleles (haplotypes) that were found expanded in affected family members. In contrast to the pure intermediate alleles, the CCGCTG intermediate repeats within families did not show intergenerational variability in size. Furthermore, we showed that the CCGCTG interrupted intermediate alleles have an allele frequency of approximately 0.35% in the general population, while CCGCTG interruptions were not detected in pathogenic repeat expansions over 50 repeat units in our control cohort. We postulate that intermediate repeats of size 37-43 having CCGCTG interruptions are not prone to further expansion, and therefore not act as premutations, which has great relevance for individuals with these alleles and has implications for genetic counseling and testing.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583464","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":"Estimating the use of biological samples in Finnish biobanks and hospital collections.","authors":"Aaro Tupasela, Tom Southerington, Johanna Mäkelä, Lila Kallio, Merja Perälä, Veli-Matti Kosma, Arto Mannermaa, Tiina Jokela, Kimmo Pitkänen, Mika Kontro, Tiina Vesterinen, Eero Punkka, Theresa Knopp, Minna Ruddock, Raisa Serpi, Anne-Mari Moilanen, Leena Viiri, Sanna Siltanen, Enni Makkonen, Päivi Ingalsuo","doi":"10.1038/s41431-025-01906-w","DOIUrl":"https://doi.org/10.1038/s41431-025-01906-w","url":null,"abstract":"<p><p>Finland has steadily developed its biobanking infrastructures since the early 2010s. This article presents a systematic overview of the number of biological samples that have been provided for research since 2013 when the Finnish Biobank Act came into force. Using data from individual biobanks and from permits issued by Fimea (formerly Valvira), we present the most up-to-date and complete account of sample use at a national level. Between 2014 and 2023 a total of 1,474,881 samples were provided through 998 sample requests. A better understanding of the use of biological samples at the national level can help highlight the important impact biobanking has as an infrastructure for supporting research. We argue that developing standards can help in developing national biobanking strategies and identify areas where biobanking can be further developed. We also conclude that the ability to combine tissue samples and health data flexibly and efficiently is essential and needs to be secured also within the context of the European Health Data Space (EHDS).</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567302","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":"A homozygous frameshift variant in the CILK1 gene causes cranioectodermal dysplasia","authors":"Abdullah Sezer,&nbsp;Sukru S. Oner,&nbsp;Hanife Saat,&nbsp;Merve G. Turan,&nbsp;Tulin Gungor,&nbsp;Sebiha Cevik,&nbsp;Asli Erol,&nbsp;Ferhan Yenisert,&nbsp;Kerem Catalbas,&nbsp;Derya Hazal Ozbakir,&nbsp;Sinem Kocagil,&nbsp;Oğuz Cilingir,&nbsp;Mehmet Ali Ergun,&nbsp;Oktay I. Kaplan","doi":"10.1038/s41431-025-01902-0","DOIUrl":"10.1038/s41431-025-01902-0","url":null,"abstract":"Cranioectodermal dysplasia (CED) is a ciliopathy characterized by skeletal and ectodermal abnormalities, renal failure, and liver fibrosis. Pathogenic variants in genes that encode the intraflagellar transport (IFT) complex components, particularly IFT-A, are responsible for approximately two-thirds of the CED cases. However, the cause of the remaining cases remains unknown. Ciliogenesis-associated kinase 1 (CILK1) is a highly conserved ciliary serine/threonine kinase with an N-terminal catalytic domain responsible for kinase activity and a C-terminal non-catalytic domain that interacts with the IFT-B complex. Biallelic variants in the catalytic domain are associated with lethal skeletal dysplasia, endocrine cerebroosteodysplasia, and short-rib polydactyly syndrome. No human disease has been linked to biallelic variants in the non-catalytic domain. We present a homozygous frameshift variant in the CILK1 gene that affects the distal part of the non-catalytic domain, causing CED in five patients from two pedigrees. All the patients survived into childhood and had disproportionately short stature, skeletal abnormalities, ectodermal dysplasia, renal issues, and liver complications. Functional data from patient-derived cells and the C. elegans model indicate that the variant reduces cilia number, increases cilia length, and disrupts the localization of IFT components. In contrast, the ciliary localization of CILK1 bearing the variant itself remains unaffected. Notably, we rescued the majority of these abnormalities by reintroducing CILK1 into patient-derived cells. Finally, our study describes CILK1 as a novel causal gene and the first non-IFT protein-encoding gene in the etiology of CED, thus expanding the known genotypic, mechanistic, and phenotypic spectrum of CED.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 10","pages":"1240-1251"},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01902-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564714","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":"Summer reading 2025 in EJHG","authors":"Alisdair McNeill","doi":"10.1038/s41431-025-01897-8","DOIUrl":"10.1038/s41431-025-01897-8","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 7","pages":"825-825"},"PeriodicalIF":3.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41431-025-01897-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559603","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":"The role of untranslated region variants in Mendelian disease: a review","authors":"Nechama Wieder,&nbsp;Elston N. D’Souza,&nbsp;Ruebena Dawes,&nbsp;Alexander Chan,&nbsp;Alexandra Martin-Geary,&nbsp;Nicola Whiffin","doi":"10.1038/s41431-025-01905-x","DOIUrl":"10.1038/s41431-025-01905-x","url":null,"abstract":"Untranslated regions (UTRs) flank the protein-coding sequence of a gene. 5′UTR and 3′ UTR sequences mediate post-transcriptional regulation via linear and structural elements, controlling RNA stability, cellular localisation and the rate of protein translation. Variants within both 5′ and 3′ UTRs have been shown to cause disease through a variety of diverse mechanisms. However, for these variants to be routinely annotated and interpreted in clinical genetic testing, we need a better understanding of these regions and the spectrum of disease-causing variants within them. In this review, we systematically assess previously identified Mendelian disease-causing variants within UTRs and catalogue their underlying mechanisms. With genome sequencing becoming readily available and increasingly incorporated in diagnostic settings, this review will provide a valuable resource for the consideration and interpretation of UTR variants.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 9","pages":"1096-1105"},"PeriodicalIF":4.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559602","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":"The European Certificate in Medical Genetics and Genomics (ECMGG)","authors":"Peter D. Turnpenny,&nbsp;Laura Pölsler,&nbsp;Ute Moog,&nbsp;Edward S. Tobias,&nbsp;Angela Peron,&nbsp;Susanne E. Boonen,&nbsp;Bonnie Lynch,&nbsp;Jonathan Berg","doi":"10.1038/s41431-025-01889-8","DOIUrl":"10.1038/s41431-025-01889-8","url":null,"abstract":"The European Certificate in Medical Genetics and Genomics (ECMGG) is the official knowledge-based, end-of-specialist training examination designed and delivered by the Union Européenne des Médecins Spécialistes – Section of Medical Genetics (UEMS-SMG). The examination is a joint venture of the SMG, the European Society of Human Genetics (ESHG), and the European Board of Medical Genetics (EBMG). Sittings have taken place in 2019 and 2021–24, and it is gaining in reputation as a high-quality, high-standard assessment. In 2024 the ECMGG underwent satisfactory appraisal by the UEMS-Council of European Specialist Medical Assessment (CESMA). This paper describes the development of the ECMGG, its structure, outcomes, and its meaning for the standards and harmonisation of the specialty of Medical Genetics throughout Europe.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 9","pages":"1113-1120"},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01889-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539684","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":"A systematic review of consumers' knowledge, attitudes and experiences of primary health professionals' role in genomic medicine.","authors":"Samran Sheriff, Maryam Vizheh, Romika Patel, Samantha Spanos, Klay Lamprell, Jeffrey Braithwaite, Janet C Long","doi":"10.1038/s41431-025-01904-y","DOIUrl":"https://doi.org/10.1038/s41431-025-01904-y","url":null,"abstract":"<p><p>The integration of genetic testing into primary care is influencing healthcare practices, yet little is known about consumers' knowledge, attitudes, and experiences with genetic testing services or the practitioners who provide them. This systematic review synthesizes peer-reviewed studies on consumers' perspectives regarding the role of primary health professionals in delivering genomic medicine in primary care settings. Six databases (PubMed, Scopus, Embase, CINAHL, Cochrane Library and PsycINFO) were systematically searched. Inclusion criteria focused on studies that addressed consumers' knowledge, attitudes, and experiences related to Primary Care Providers' (PCP) roles in genomic medicine. Data relevant to the review objective, including key article characteristics, barriers and facilitators of implementation, and recommendations for advancement or optimisation, were extracted and analysed using thematic analysis. We reviewed 19 studies meeting the inclusion criteria involving 3557 participants. Thematic analysis identified two overarching themes: consumer views on genomic testing irrespective of setting, comprising three sub-themes, and consumer views on genomic testing in the primary care setting, comprising four sub-themes. Consumers' trust in PCPs as familiar and approachable professionals was a major concern. Consumers often reported positive experiences when PCPs were well-informed and communicative, but negative experiences were common when there was a perceived lack of knowledge or confidence from the PCP. As reported in other healthcare settings, concerns about privacy, data security, and the cost of genomic testing were also prominent. Integrating genomic medicine into primary care requires trust-building between PCPs and consumers, enhancing PCP education and resources, addressing privacy and cost concerns and strengthening collaboration with genetic specialists to improve consumer experiences.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552762","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":"European training requirements for the specialty of medical genetics","authors":"Ute Moog,&nbsp;Jonathan Berg,&nbsp;Siobhan Kerr,&nbsp;Peter D. Turnpenny,&nbsp;Alain Verloes,&nbsp;Working Group ETR for Medical Genetics,&nbsp;Johannes Zschocke","doi":"10.1038/s41431-025-01899-6","DOIUrl":"10.1038/s41431-025-01899-6","url":null,"abstract":"The development of European training standards is a major contribution to the improvement of medical training at the European level and one of the core activities of the European Union of Medical Specialists (Union Européenne des Médecins Spécialistes, UEMS). European Training Requirements for the specialty of Medical Genetics (ETR-MG) were first developed and approved in 2017. Here we report the content and objectives of the 2023 revision, carried out by the ETR-MG Working Group and the officers of the UEMS Section of Medical Genetics in close cooperation with the ESHG and the European Board of Medical Genetics (EBMG). New aspects concern an update of the description of the specialty, the integration of the examination for the European Certificate in Medical Genetics and Genomics (ECMGG), a complete restructuring of the syllabus, and the adaption to novel concepts of medical education.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 9","pages":"1121-1126"},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01899-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552763","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":"Incorporating biobanking into the future of healthcare: exploring patient and healthcare worker perspectives at a Canadian tertiary academic hospital","authors":"Sila Usta,&nbsp;Noor Kundu,&nbsp;Dylan Gowlett-Park,&nbsp;August Lin,&nbsp;Alexandra Misura,&nbsp;Katarina Czibere,&nbsp;Liying Zhang,&nbsp;Olga Bigun,&nbsp;Renato Sasso,&nbsp;Thibika Gunalingam,&nbsp;Winston Ukpong,&nbsp;Tina Khazaee,&nbsp;Betty Wong,&nbsp;Samuel Matsumura,&nbsp;Hubert Tsui,&nbsp;Signy Chow","doi":"10.1038/s41431-025-01898-7","DOIUrl":"10.1038/s41431-025-01898-7","url":null,"abstract":"Biobanks are an essential resource for researchers conducting scientific and translational research but require significant support from institutions and healthcare workers (HW) to operate and are reliant on patient consent and participation. In order to better understand the barriers to institution-wide biobanking, we conducted a survey to examine the knowledge, attitudes and concerns of patients and HW on a range of biobanking-related topics, including consenting practices, privacy and trust in the healthcare team and researchers, and current practices at Sunnybrook Health Sciences Centre. Overall, we found that there is strong patient and HW support for biobanking as a resource for research (89–96%). Furthermore, the majority 53% of HW are willing to incorporate biobanking into their clinical workflow and 39% had a neutral response. Encouragingly, patients possess a high level of trust in their healthcare team (80-99%). The main concerns regarding sample donation were ‘breaches of privacy’ and ‘genetic information being used in an exclusionary (discriminatory) fashion.’ Concerns around specimen utilization emerged as a major theme from HW. These results will inform and enhance future biobanking practices to improve the patient experience and increase patient engagement while streamlining specimen collection and utilization for scientific research.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 9","pages":"1194-1202"},"PeriodicalIF":4.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01898-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527025","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}