European Journal of Human Genetics最新文献_第8页

Strømme syndrome: the clinical and molecular spectrum associated with variants in CENPF Strømme综合征：与CENPF变异相关的临床和分子谱

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2026-07-18 DOI: 10.1038/s41431-026-02187-7

Meghan R. Mulligan, Heather Mulhall, Samuel R. A. Hawarden, David Davies-Payne, Raoul Heller, Louise S. Bicknell

{"title":"Strømme syndrome: the clinical and molecular spectrum associated with variants in CENPF","authors":"Meghan R. Mulligan, Heather Mulhall, Samuel R. A. Hawarden, David Davies-Payne, Raoul Heller, Louise S. Bicknell","doi":"10.1038/s41431-026-02187-7","DOIUrl":"10.1038/s41431-026-02187-7","url":null,"abstract":"Strømme syndrome (MIM 243605) or a form of syndromic microcephaly have both been reported to be caused by biallelic variants in CENPF. The common features associated with CENPF variants are microcephaly, jejunal atresia and eye abnormalities, but additional case reports have indicated more variable presentations. Here, we describe the diagnosis of an adult with Strømme syndrome and present a review of all 32 cases reported with genetic variants in CENPF, to highlight the common and diverse features. We find that neurological abnormalities, particularly microcephaly, are the most common feature (91% of individuals), with gastrointestinal (69%) and ocular features (44%) less common. While facial dysmorphism is widely reported, there are a broad variety of features noted, with no clear commonalities. The vast majority of genetic variants identified alter the reading frame through either nonsense, frameshift, or more rarely, essential splice site variants. Missense variants are seldomly reported; all are homozygous in affected individuals, but functional evidence has been presented for only one missense variant. Our summary illustrates the breadth of clinical features associated with Strømme syndrome caused by CENPF variants and the molecular genetics of CENPF reported thus far.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"34 10","pages":"1486-1492"},"PeriodicalIF":4.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-026-02187-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497279","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}

引用次数: 0

A thick opt-out for genomic newborn screening, retention, and reuse of genomic data. 基因组新生儿筛选、保留和基因组数据重用的厚选择。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2026-07-17 DOI: 10.1038/s41431-026-02193-9

Eline M Bunnik

引用次数: 0

ERN GENTURIS cancer surveillance guideline for individuals with PTEN hamartoma tumour syndrome (PHTS). 针对PTEN错构瘤肿瘤综合征（PHTS）患者的ERN GENTURIS癌症监测指南。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2026-07-16 DOI: 10.1038/s41431-026-02181-z

Nicoline Hoogerbrugge, Ana Blatnik, Charlotte Kvist Lautrup, Robert Hüneburg, Daniela Turchetti, Anne van Altena, Frédéric Caux, Sophie Da Mota Gomes, Kelly Kearley, Chella Rs van der Post, Alex Teulé, Jolanda Schieving, Inga-Lena Nilsson, Ritse Mann, Per-Olof Lundgren, Thera Links, Emma Tham, Sjaak Pouwels, Marc Tischkowitz

{"title":"ERN GENTURIS cancer surveillance guideline for individuals with PTEN hamartoma tumour syndrome (PHTS).","authors":"Nicoline Hoogerbrugge, Ana Blatnik, Charlotte Kvist Lautrup, Robert Hüneburg, Daniela Turchetti, Anne van Altena, Frédéric Caux, Sophie Da Mota Gomes, Kelly Kearley, Chella Rs van der Post, Alex Teulé, Jolanda Schieving, Inga-Lena Nilsson, Ritse Mann, Per-Olof Lundgren, Thera Links, Emma Tham, Sjaak Pouwels, Marc Tischkowitz","doi":"10.1038/s41431-026-02181-z","DOIUrl":"10.1038/s41431-026-02181-z","url":null,"abstract":"PTEN hamartoma tumour syndrome (PHTS) is a diverse multi-system disorder predisposing to a high hereditary risk of breast, thyroid, endometrial, and a moderate risk of renal, and colorectal cancer and skin melanoma. Besides the risk of cancer, PHTS is also associated with benign tumours such as skin and connective tissue tumours, vascular malformations and neurodevelopmental disorders, including autism spectrum disorders. New evidence on cancer risks and the effectiveness of surveillance has been published since the last iteration of the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS) guidelines from 2020, necessitating the update presented here A comprehensive literature review was undertaken, and guidelines were revised by clinicians with PHTS expertise from relevant medical disciplines, together with PHTS patients and their representatives. Revised recommendations were put forward for surveillance for breast, thyroid, endometrial, renal, and colorectal cancer and skin melanoma. The proposed cancer surveillance recommendations for PHTS require significant patient commitment as well as a coordinated multidisciplinary medical approach. There is a need for prospective evaluation of the effectiveness of these recommendations in the PHTS population.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469726","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}

引用次数: 0

Correction: Psychosocial outcomes of reproductive genetic carrier screening up to five years post-result. 更正：生殖基因携带者筛查结果后5年的社会心理结果。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2026-07-15 DOI: 10.1038/s41431-026-02186-8

Erin Tutty, Alison D Archibald, Belinda J Dawson-McClaren, Cameron Patrick, Martin B Delatycki, Sharon Lewis

引用次数: 0

Unveiling ocular developmental disorders through short-read whole-genome sequencing 通过短读全基因组测序揭示眼部发育障碍。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2026-07-14 DOI: 10.1038/s41431-026-02160-4

AURAGEN consortium

{"title":"Unveiling ocular developmental disorders through short-read whole-genome sequencing","authors":"AURAGEN consortium","doi":"10.1038/s41431-026-02160-4","DOIUrl":"10.1038/s41431-026-02160-4","url":null,"abstract":"Congenital eye malformations represent a clinically and genetically heterogeneous group of disorders. Despite advances in genetic testing, fewer than half of affected patients receive a definitive molecular diagnosis. However, obtaining a molecular diagnosis is crucial for these patients and their families. Whole genome sequencing (WGS) is now standard practice in the genetic investigation of patients, but its contribution has not been extensively evaluated in patients with ocular malformations. In this work, we performed short-read WGS in a cohort of 100 families presenting with eye developmental disorders, including microphthalmia-anophthalmia spectrum (M/A), coloboma, anterior segment dysgenesis, congenital cataracts and/or foveal hypoplasia. Prior to WGS, 47 individuals had undergone targeted next-generation sequencing (NGS) of genes panels related to ocular development, 11 had chromosomal microarray analysis (CGH-array) and 20 had a combination of both. None had received a definitive genetic diagnosis. WGS identified a (likely) pathogenic variant in eighteen patients. In addition, candidate variants of uncertain significance were detected in nine patients. Notably, fourteen of these variants would have been missed by conventional genes panels or CGH-array, underscoring the broader diagnostic scope of WGS. Our findings demonstrate that short-read WGS significantly improves diagnostic yield in patients with congenital eye malformations, including those previously undiagnosed despite NGS panel testing. These results support the integration of WGS in the genetic evaluation of ocular developmental disorders.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"34 10","pages":"1573-1584"},"PeriodicalIF":4.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-026-02160-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445206","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}

引用次数: 0

Family-oriented support in genetic counselling: a scoping review of clinical practice and psychotherapeutic interventions. 以家庭为导向的遗传咨询支持：临床实践和心理治疗干预的范围审查。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2026-07-13 DOI: 10.1038/s41431-026-02165-z

Claire E Green, Joanna Smith, Hilary Piercy

{"title":"Family-oriented support in genetic counselling: a scoping review of clinical practice and psychotherapeutic interventions.","authors":"Claire E Green, Joanna Smith, Hilary Piercy","doi":"10.1038/s41431-026-02165-z","DOIUrl":"https://doi.org/10.1038/s41431-026-02165-z","url":null,"abstract":"Families living with inherited genetic conditions (IGCs) face practical and emotional challenges that affect individual well-being and family relationships. Although genetic counselling recognises the familial nature of genomic risk, support is often limited to patient-led disclosure. This scoping review examined how family-oriented support is conceptualised, delivered, and evaluated within genetic counselling and related psychosocial services. We define family-oriented support as any practice that explicitly considers relatives and family relationships, and systemic family-oriented care as family-systems-based models treating the family as the unit of care. Following PRISMA-ScR guidance, seven databases were searched to August 2025 for publications describing practices or interventions with a clear family element in services for people living with IGCs. Data were charted descriptively and synthesised using Rolland's Family Systems Illness/Family Systems Genetic Illness (FSI/FSGI) frameworks. Thirty-three publications were included, describing (1) clinical practice with a family element (n = 12), mainly strategies to promote intrafamilial communication, and (2) psychotherapeutic approaches (n = 21), ten of which had been formally evaluated. Qualitative evidence suggested perceived psychosocial benefits, whereas quantitative findings were modest or mixed, constrained by small samples and limited follow-up. Most activity reflected relatively early, proband-centred positions on the FSI/FSGI continuum; only a few multifamily and narrative interventions and one local service model approximated systemic family-oriented care and remained small-scale and specialist. Work focused largely on hereditary breast/ovarian cancer, with marked gaps for untreatable or unpredictable conditions, men, partners, children, and non-Western groups. Advancing systemic, family-level care will require embedding FSI/FSGI principles in training and service design and investing in longitudinal, family-level evaluation.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435736","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}

引用次数: 0

The globin depletion paradox: when short-read optimisation does not transfer to long-read RNA sequencing. 珠蛋白消耗悖论：当短读优化不转移到长读RNA测序。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2026-07-10 DOI: 10.1038/s41431-026-02184-w

Himanshu Goel

引用次数: 0

Copy number variant analysis by exome sequencing is an effective approach to optimize diagnostic yield for developmental disorders-the DDD-Africa study. 外显子组测序的拷贝数变异分析是优化发育障碍诊断率的有效方法。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2026-07-09 DOI: 10.1038/s41431-026-02179-7

Nadja Louw, Prince Makay, Phelelani T Mpangase, Barry Shingwenyana, Zandisiwe Goliath, Thirona Naicker, Laura M Yates, Engela Honey, Gerrye Mubungu, Kris Van Den Bogaert, Helen V Firth, Matthew E Hurles, Prosper Lukusa Tshilobo, Koen Devriendt, Amanda Krause, Nadia Carstens, Aimé Lumaka, Zané Lombard

{"title":"Copy number variant analysis by exome sequencing is an effective approach to optimize diagnostic yield for developmental disorders-the DDD-Africa study.","authors":"Nadja Louw, Prince Makay, Phelelani T Mpangase, Barry Shingwenyana, Zandisiwe Goliath, Thirona Naicker, Laura M Yates, Engela Honey, Gerrye Mubungu, Kris Van Den Bogaert, Helen V Firth, Matthew E Hurles, Prosper Lukusa Tshilobo, Koen Devriendt, Amanda Krause, Nadia Carstens, Aimé Lumaka, Zané Lombard","doi":"10.1038/s41431-026-02179-7","DOIUrl":"10.1038/s41431-026-02179-7","url":null,"abstract":"Copy number variants (CNV) contribute significantly to the pathogenic variation associated with developmental disorders. CNV detection is often not included in standard exome sequencing (ES) analysis. Complementary methods such as chromosomal microarray are typically offered in diagnostic laboratories to diagnose pathogenic CNV. In this study, we aimed to develop an effective approach for incorporating CNV detection within our ES analysis process for the Deciphering Developmental Disorders in Africa (DDD-Africa) cohort. We analyzed ES data from 505 probands with a developmental disorder, applying a CNV detection approach that assessed data generated using the tools CANOES and XHMM. When available, parental ES data was used to assess inheritance patterns. We confirmed a diagnosis in 41/505 (8,1%) patients with 43 pathogenic CNV identified in the probands. There were 31 deletions and 12 duplications. Among the 26 probands with parental data, all identified CNV were de novo. The addition of CNV analysis to our ES analysis pipeline resulted in an 8.1% increase in diagnostic yield in the DDD-Africa cohort without additional laboratory cost. This offers a feasible approach which is likely to reduce analytical cost and is suitable for low- and middle-income countries where funding and resources for genomic medicine initiatives are limited.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419843","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}

引用次数: 0

Whole-exome sequencing reveals novel and previously reported variants in genes linked to white matter pathology in neurodevelopmental disorders 全外显子组测序揭示了神经发育障碍中与白质病理相关的基因的新颖和先前报道的变异。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2026-07-09 DOI: 10.1038/s41431-026-02182-y

Naeem Ahmad, Tooba Aleem, Chunyu Liu, Maliha Rashid, Javeria Tehreem, Mary Ann Minal Junaid, Muhammad Farrukh Asif, Shakir Ullah, Sami Ullah, Tehseen Ullah Khan Afridi, Usman Raza Baig, Muhammad Tariq, Tahir Naeem Khan, Lydia Green, James A. Poulter, Naveed Altaf Malik

{"title":"Whole-exome sequencing reveals novel and previously reported variants in genes linked to white matter pathology in neurodevelopmental disorders","authors":"Naeem Ahmad, Tooba Aleem, Chunyu Liu, Maliha Rashid, Javeria Tehreem, Mary Ann Minal Junaid, Muhammad Farrukh Asif, Shakir Ullah, Sami Ullah, Tehseen Ullah Khan Afridi, Usman Raza Baig, Muhammad Tariq, Tahir Naeem Khan, Lydia Green, James A. Poulter, Naveed Altaf Malik","doi":"10.1038/s41431-026-02182-y","DOIUrl":"10.1038/s41431-026-02182-y","url":null,"abstract":"Functional neuronal networks are essential for brain growth and development, with myelin or “white matter” playing a key role not just in neuronal transmission but also in axonal support, maintenance, and repair. Disruption of these networks through genetic variation contributes to a range of neurodevelopmental disorders, including both primary inherited white matter disorders and an ever increasing list of secondary leukodystrophies or leucoencephalopathies. Traditionally identified using neuroimaging techniques such as magnetic resonance imaging (MRI), clinico-radiological heterogeneity means MRI alone is rarely sufficient in providing a diagnosis requiring integration with genomic techniques and expert medical review. In this study, we describe an exome-first approach in a cohort of 78 consanguineous families with undiagnosed neurodevelopmental disorders in a healthcare resource-poor setting. The aim is to demonstrate that, even in the absence of MRI imaging, we have the potential to improve diagnostic accuracy and yield. We report positive findings in six families, including known variants in MLC1, AIMP1, ASPA, and DEGS1, and novel variants in XPA and POLR3B. This study highlights the effectiveness of whole-exome sequencing as a diagnostic tool for heterogeneous neurological disorders and provides additional evidence supporting gene-disease associations in conditions linked to white matter pathology.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"34 10","pages":"1465-1472"},"PeriodicalIF":4.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-026-02182-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411082","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}

引用次数: 0

Integrative and systematic genomic approaches to improve diagnosis in rare and undiagnosed diseases: results from the RareBoost project 改善罕见和未确诊疾病诊断的综合和系统基因组方法：来自RareBoost项目的结果。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2026-07-09 DOI: 10.1038/s41431-026-02177-9

Ayca Yigit, Mert Pekerbas, Baris Salman, Kutay Bulut, Emre Ozzeybek, Mehmet Mert Topaloglu, Burcu Akman, Ravza Nur Yildirim, Sinem Aktug, Tugce Batur, Rare and Undiagnosed Diseases Advisory Board Consortium, Ugur Ozbek

{"title":"Integrative and systematic genomic approaches to improve diagnosis in rare and undiagnosed diseases: results from the RareBoost project","authors":"Ayca Yigit, Mert Pekerbas, Baris Salman, Kutay Bulut, Emre Ozzeybek, Mehmet Mert Topaloglu, Burcu Akman, Ravza Nur Yildirim, Sinem Aktug, Tugce Batur, Rare and Undiagnosed Diseases Advisory Board Consortium, Ugur Ozbek","doi":"10.1038/s41431-026-02177-9","DOIUrl":"10.1038/s41431-026-02177-9","url":null,"abstract":"Rare and undiagnosed diseases pose diagnostic challenges due to phenotypic and genetic heterogeneity and the limitations of conventional molecular testing. As part of the RareBoost project, we implemented an integrated, stepwise genomic strategy in a cohort of 134 patients from 120 families with previously inconclusive genetic testing. Our strategy combined systematic exome sequencing with subsequent genome sequencing when indicated, followed by targeted RNA-sequencing, and complemented with comprehensive phenotyping and follow-up segregation analysis. Definitive molecular diagnoses (pathogenic/likely pathogenic variants) were achieved in 25.0% of families, and an additional 25.8% harbored clinically relevant variants of uncertain significance with phenotypic correlation. This approach identified non-coding and structural variants while resolving cases through systematic reanalysis of previously negative data. Collectively, our findings demonstrate that integrated genomic and transcriptomic analyses with reanalysis of existing data enhance diagnostic yield in complex rare disease cohorts and provide a scalable framework for implementing genomic medicine in clinical practice.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"34 10","pages":"1473-1485"},"PeriodicalIF":4.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419828","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}

引用次数: 0