European Journal of Human Genetics最新文献_第3页

Prenatal Variants of Uncertain Significance (VUS): to report or not to report? 产前不确定意义变异（VUS）：报告还是不报告？

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-08-21 DOI: 10.1038/s41431-025-01924-8

Maayke A. de Koning, Malgorzata I. Srebniak, Esther J. Oldekamp, Denise Hahn, Karin E. M. Diderich, Hennie T. Bruggenwirth, Gijs W. E. Santen, Mariëtte J. V. Hoffer, Manon Suerink

{"title":"Prenatal Variants of Uncertain Significance (VUS): to report or not to report?","authors":"Maayke A. de Koning, Malgorzata I. Srebniak, Esther J. Oldekamp, Denise Hahn, Karin E. M. Diderich, Hennie T. Bruggenwirth, Gijs W. E. Santen, Mariëtte J. V. Hoffer, Manon Suerink","doi":"10.1038/s41431-025-01924-8","DOIUrl":"10.1038/s41431-025-01924-8","url":null,"abstract":"Prenatal Exome Sequencing (pES) has a significant diagnostic yield but time pressure and limited phenotypic information make interpretation of Variants of Uncertain Significance (VUS) more challenging than in a postnatal setting. We share our experiences of prenatal reporting of highly suspicious VUS. We retrospectively analyzed pregnancies in which VUS identified by pES were reported to parents during pregnancy in two Dutch academic medical hospitals. During the study period, 31 VUS in 28 genes were reported in 27 pregnancies. Cases were assigned to one of five groups based on consistency of prenatal phenotypes with gene-associated diagnoses. The implications of VUS included clinical evaluation of parental carriers (N = 4), additional screening of proband (N = 2), influencing parental decision-making (N = 11) and/or prompting confirmatory testing (N = 10). Reanalysis with currently available data resulted in reclassification of seven variants, five of which were upgraded to (likely) pathogenic. Although we do not recommend routine disclosure, our data suggest that prenatal reporting of VUS can be valuable in exceptional cases. Stringent selection was applied and only a minority of reported VUS was reclassified as (likely) pathogenic. Therefore, a careful individual assessment of each VUS case remains imperative and multidisciplinary meetings should be an integral part of prenatal VUS management.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 10","pages":"1300-1308"},"PeriodicalIF":4.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947799","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

EMQN best practice guidelines for analysis and reporting of microsatellite instability in solid tumours. EMQN实体肿瘤微卫星不稳定性分析和报告最佳实践指南。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-08-20 DOI: 10.1038/s41431-025-01913-x

Richard Gallon, Liam McCormick, Angelica Saetta, Cristina Albuquerque, Samantha Butler, Treena Cranston, Joanne Field, Ciaron McAnulty, Patrícia Silva, Melanie Cheetham, Katie Sheils, George J Burghel

{"title":"EMQN best practice guidelines for analysis and reporting of microsatellite instability in solid tumours.","authors":"Richard Gallon, Liam McCormick, Angelica Saetta, Cristina Albuquerque, Samantha Butler, Treena Cranston, Joanne Field, Ciaron McAnulty, Patrícia Silva, Melanie Cheetham, Katie Sheils, George J Burghel","doi":"10.1038/s41431-025-01913-x","DOIUrl":"https://doi.org/10.1038/s41431-025-01913-x","url":null,"abstract":"Microsatellite instability (MSI) is the accumulation of insertion and deletion variants (instability) in short tandem repeat DNA sequences (microsatellites). High levels of MSI occur following loss of function of the DNA mismatch repair system (MMR). MMR deficiency is an increasingly important cancer biomarker that is associated with chemotherapy resistance and response to immune checkpoint blockade, as well as one of the commonest hereditary cancer syndromes, Lynch syndrome. Since its discovery over two decades ago, our biological understanding, the testing methods, and the clinical implications of MSI analysis have expanded rapidly and up-to-date best practice guidelines are needed. An expert working group reviewed the literature and devised 15 best practice recommendations that were finalised following consultation with clinical and laboratory scientists partnered with EMQN. These include seven recommendations on key technical aspects of MSI testing and eight recommendations on the clinical interpretation and reporting of results. The latter focuses on Lynch syndrome screening and immune checkpoint blockade therapy. Example report wording is provided to assist implementation and standardisation. Common terminology and MSI analysis methods are also discussed. These guidelines are aimed primarily at genomic scientists working in diagnostic testing laboratories, but will provide a useful review of MSI for clinicians, academics, and other related professionals.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947818","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

MINDDS-connect: a federated data platform integrating biobanks for meta cohort building and analysis. MINDDS-connect：一个联邦数据平台，集成生物库，用于元队列构建和分析。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-08-20 DOI: 10.1038/s41431-025-01927-5

Benjamin Huremagic, Nishkala Sattanathan, Mathilde Geysens, Janet Harwood, Jente Verbesselt, Senne Meynants, Ann Swillen, Kris Van Den Bogaert, Danijela Drakulic, Goran Cuturilo, Thérèse van Amelsvoort, David Linden, Natália Oliva-Teles, Paula Jorge, Marianne B M van den Bree, Jessica H Hall, Haleh Chizari, Amin Ardeshirdavani, Adrian J Harwood, Geert Vandeweyer, Yves Moreau, Joris Robert Vermeesch

{"title":"MINDDS-connect: a federated data platform integrating biobanks for meta cohort building and analysis.","authors":"Benjamin Huremagic, Nishkala Sattanathan, Mathilde Geysens, Janet Harwood, Jente Verbesselt, Senne Meynants, Ann Swillen, Kris Van Den Bogaert, Danijela Drakulic, Goran Cuturilo, Thérèse van Amelsvoort, David Linden, Natália Oliva-Teles, Paula Jorge, Marianne B M van den Bree, Jessica H Hall, Haleh Chizari, Amin Ardeshirdavani, Adrian J Harwood, Geert Vandeweyer, Yves Moreau, Joris Robert Vermeesch","doi":"10.1038/s41431-025-01927-5","DOIUrl":"https://doi.org/10.1038/s41431-025-01927-5","url":null,"abstract":"Access to large patient cohort data and biobanked resources is a catalyst for progress in genomics and biomedical research, increasing statistical power, and unlocking deeper insights-especially in areas like rare diseases and mental health. Responsible research necessitates maintenance of data privacy, regulatory compliance, and research standardization. It can appear that these guiding principles oppose each other and present barriers to responsible Open science. To address these critical challenges, we developed MINDDS-Connect, a federated data collaboration platform that integrates a web-based interface with decentralized Docker instances via a REST API. This architecture allows registered users to securely query samples across the platform's network, and offers a tool to facilitate the formation of virtual multi-centric meta-cohorts and research collaboration. MINDDS-Connect allows institutions to retain data control while enabling collaborative research and meta-cohort analysis through standardized metadata fields. Its implementation across five European centers enhanced the accessibility of 900 samples, demonstrating its effectiveness in enabling cohort construction and promoting collaborative research. The platform provides a secure, open-source solution consistent with EU Open Science policies, advancing large-scale mental health research.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947872","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

Neurobehavioral profile of individuals with pathogenic variants in CHD3 CHD3致病性变异个体的神经行为特征。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-08-19 DOI: 10.1038/s41431-025-01926-6

Anca Ionescu, Emmanuelle Mazur-Lainé, Mélodie Proteau-Lemieux, Inga S. Knoth, Keely Vachon, Kerri Whitlock, Hazel Maridith Barlanhan Biag, Nazim Rabouhi, Hendrikus J. Van Heesbeen, Sébastien Jacquemont, David Hessl, Leonard Abbeduto, Evdokia Anagnostou, François Bolduc, Randi J. Hagerman, Philippe M. Campeau, Sarah Lippé

{"title":"Neurobehavioral profile of individuals with pathogenic variants in CHD3","authors":"Anca Ionescu, Emmanuelle Mazur-Lainé, Mélodie Proteau-Lemieux, Inga S. Knoth, Keely Vachon, Kerri Whitlock, Hazel Maridith Barlanhan Biag, Nazim Rabouhi, Hendrikus J. Van Heesbeen, Sébastien Jacquemont, David Hessl, Leonard Abbeduto, Evdokia Anagnostou, François Bolduc, Randi J. Hagerman, Philippe M. Campeau, Sarah Lippé","doi":"10.1038/s41431-025-01926-6","DOIUrl":"10.1038/s41431-025-01926-6","url":null,"abstract":"Snijders Blok-Campeau syndrome (SNIBCPS), a neurodevelopmental disorder first described in 2018, is caused by heterozygous pathogenic variants in CHD3. Its encoded protein plays a crucial role in the development of the nervous system of embryos. While phenotypic traits have been broadly defined, i.e., global neurodevelopmental delays such as intellectual disabilities and delayed speech acquisition, and physical features such as characteristic facial features and macrocephaly, the phenotypic spectrum has not been further assessed. We present the neurobehavioral profile of 38 individuals with variants in CHD3 and compare it to the ones of autism spectrum disorder (ASD) and Fragile X syndrome (FXS) cohorts. Profound clinical deficits were found in adaptive functioning, communication skills, and sensorimotor functioning in most SNIBCPS participants. Similarities between FXS and SNIBCPS cohorts were unveiled, characterized by diminished levels of global adaptive behavior and adaptive functioning in the social and communication domains. Nevertheless, despite profound challenges in global adaptive behavior in SNIBCPS, we reveal the social domain as showing the highest adaptive levels alongside minimal emotional/behavioral issues within the sample, suggesting relative strengths inherent to SNIBCPS. This study enriches the scarce SNIBCPS literature by delineating the neurobehavioral phenotypic spectrum of SNIBCPS and by innovating comparisons with clinically akin neurodevelopmental disorders.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 10","pages":"1350-1358"},"PeriodicalIF":4.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882500","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

Non-isolated tetralogy of fallot (TOF+): exome sequencing efficacy and phenotypic expansions. 非分离法洛四联症（TOF+）：外显子组测序效果和表型扩增。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-08-12 DOI: 10.1038/s41431-025-01916-8

Julia Volpi, Xiaonan Zhao, Nichole Owen, Tia Evans, Muriel Holder-Espinasse, Nayana Lahiri, Eleanor Sherlock, Gemma Poke, Jeroen Breckpot, Koen Devriendt, Bjorn Cools, Alfredo Brusco, Giovanni Battista Ferrero, Enrico Grosso, Pradeep Vasudevan, Sara Loddo, Antonio Novelli, Maria Cristina Digilio, Aafke Engwerda, Marrit Hitzert, Alison Male, Lucy Bownass, Ruth Newbury-Ecob, Zosia Miedzybrodzka, Ruth Armstrong, Sally Ann Lynch, Gunnar Houge, Shiyi Xiong, Seema R Lalani, Jill A Rosenfeld, Pamela N Luna, Chad A Shaw, Daryl A Scott

{"title":"Non-isolated tetralogy of fallot (TOF+): exome sequencing efficacy and phenotypic expansions.","authors":"Julia Volpi, Xiaonan Zhao, Nichole Owen, Tia Evans, Muriel Holder-Espinasse, Nayana Lahiri, Eleanor Sherlock, Gemma Poke, Jeroen Breckpot, Koen Devriendt, Bjorn Cools, Alfredo Brusco, Giovanni Battista Ferrero, Enrico Grosso, Pradeep Vasudevan, Sara Loddo, Antonio Novelli, Maria Cristina Digilio, Aafke Engwerda, Marrit Hitzert, Alison Male, Lucy Bownass, Ruth Newbury-Ecob, Zosia Miedzybrodzka, Ruth Armstrong, Sally Ann Lynch, Gunnar Houge, Shiyi Xiong, Seema R Lalani, Jill A Rosenfeld, Pamela N Luna, Chad A Shaw, Daryl A Scott","doi":"10.1038/s41431-025-01916-8","DOIUrl":"10.1038/s41431-025-01916-8","url":null,"abstract":"Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect (CHD). TOF may present in isolation or in conjunction with one or more non-cardiac congenital anomalies or neurodevelopmental disorders (TOF+). Uncertainty regarding the efficacy of various genetic testing strategies, and an incomplete understanding of the genetic causes of TOF+, may lead to hesitancy in recommending genetic testing, particularly, clinical exome sequencing (cES). Here, we analyzed cES data from 131 individuals with TOF+. A definitive or probable diagnosis was made for 31 individuals, yielding a diagnostic rate of 23.6% (31/131). One individual received three diagnoses. Commercially available CHD panels would have detected only 27.3% (9/33) to 63.6% (21/33) of the diagnoses made by cES. We then used a machine learning approach to identify four genes for which there is sufficient evidence to support a phenotypic expansion including TOF: DVL3, MED13L, PUF60, and MEIS2. Since chromosomal microarray analysis (CMA) has been reported to have a diagnostic efficacy of 10-20% in individuals with TOF, we conclude that cES should be considered for all individuals with TOF+ for whom a molecular diagnosis has not been established by CMA. We also conclude that TOF represents a low penetrance phenotype associated with genetic syndromes caused by pathogenic variants in DVL3, MED13L, PUF60, and MEIS2.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834609","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

Machine learning predicts distinct biotypes of amyotrophic lateral sclerosis 机器学习预测肌萎缩性侧索硬化症的不同生物类型。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-08-07 DOI: 10.1038/s41431-025-01920-y

Nicholas Pasternack, Ole Paulsen, Avindra Nath

引用次数: 0

Genomic medicine in full bloom: a summer farewell issue 盛放的基因组医学：夏季告别刊

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-08-04 DOI: 10.1038/s41431-025-01914-w

Seda Sinem Zonuzi, Alisdair McNeill

引用次数: 0

Biallelic MED29 variants cause pontocerebellar hypoplasia with cataracts 双等位基因MED29变异引起桥小脑发育不全伴白内障。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-31 DOI: 10.1038/s41431-025-01918-6

Leo Arkush, Geeske M. van Woerden, Limor Ziv, Dina Marek-Yagel, Reginald Fonseca, Esmee Brevé, Ortal Barel, Nechama Shalva, Alvit Veber, Yair Anikster, Dominique Ben-Ami Raichman, Banan Musallam, Shai Marcu, Andreea Nissenkorn, Hanna Mandel, Steven A. Kushner, Bruria Ben Zeev, Gali Heimer

{"title":"Biallelic MED29 variants cause pontocerebellar hypoplasia with cataracts","authors":"Leo Arkush, Geeske M. van Woerden, Limor Ziv, Dina Marek-Yagel, Reginald Fonseca, Esmee Brevé, Ortal Barel, Nechama Shalva, Alvit Veber, Yair Anikster, Dominique Ben-Ami Raichman, Banan Musallam, Shai Marcu, Andreea Nissenkorn, Hanna Mandel, Steven A. Kushner, Bruria Ben Zeev, Gali Heimer","doi":"10.1038/s41431-025-01918-6","DOIUrl":"10.1038/s41431-025-01918-6","url":null,"abstract":"Pontocerebellar hypoplasia (PCH) represents a group of disorders characterized by cerebellum and pons hypoplasia, variable cerebral involvement, microcephaly, severe global developmental delay (GDD), and seizures. We sought the genetic cause of PCH in two siblings. Genetic workup was performed by whole-exome sequencing followed by Sanger validation. Morpholino-knockdown zebrafish embryos with human wild-type gene rescue were used to assess cerebellar development and motor function. Transfected mouse hippocampal cultures and electroporated mouse embryos were employed to assess functional effects on neuronal morphology and development. Both patients presented with profound GDD, severe microcephaly, cataracts, and variably seizures. Their MRIs demonstrated marked cerebellar and pontine hypoplasia. Both were homozygous for a c.416T > C, p.(Leu139Pro) MED29 variant which was predicted to be pathogenic. Locomotion and cerebellar GABAergic neurons development were both impaired in MED29 Morpholino-knockdown zebrafish and rescued by human wild-type gene expression. ShRNA-knockdown of MED29 in mouse hippocampal neurons decreased neurite length and arborization in vitro, and caused defective embryonic neuronal migration in vivo. Overexpression of MED29 p.(Leu139Pro) was consistent with a loss-of-function. Taken together, the Mediator complex regulates transcription processes, and defects in particular subunits are associated with distinct neurodevelopmental phenotypes involving PCH. We conclude that MED29 is a novel risk gene for PCH.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 10","pages":"1271-1280"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01918-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759561","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

Direct letters to relatives at risk of hereditary cancer—a randomised trial on healthcare-assisted versus family-mediated risk disclosure 直接写信给有遗传性癌症风险的亲属——一项关于医疗辅助与家庭介导风险披露的随机试验。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-31 DOI: 10.1038/s41431-025-01922-w

Hans Ehrencrona, Anna Öfverholm, Carolina Hawranek, Lovisa Lovmar, Sara Svensson, Sigrid Wennstedt, Barbro Hellquist, Anna Rosén

{"title":"Direct letters to relatives at risk of hereditary cancer—a randomised trial on healthcare-assisted versus family-mediated risk disclosure","authors":"Hans Ehrencrona, Anna Öfverholm, Carolina Hawranek, Lovisa Lovmar, Sara Svensson, Sigrid Wennstedt, Barbro Hellquist, Anna Rosén","doi":"10.1038/s41431-025-01922-w","DOIUrl":"10.1038/s41431-025-01922-w","url":null,"abstract":"Observational studies suggest that direct contact from healthcare to at-risk relatives may increase genetic counselling (GC) uptake as compared to family-mediated risk disclosure, but randomised controlled trials (RCTs) are lacking. This study assessed whether the offer of direct letters to relatives at risk of hereditary breast and ovarian cancer (HBOC) or Lynch syndrome increases GC uptake compared to family-mediated communication alone. Between 2020 and 2023, probands were randomly assigned to family-mediated disclosure (control) or family-mediated disclosure plus the offer of sending direct letters to at-risk relatives (intervention). The primary outcome was GC uptake within 12 months, measured as the proportion of eligible relatives at risk contacting a Swedish cancer genetics clinic. In total, 165 families (median: 4 eligible relatives, range: 1–26) were randomised to control (n = 79) or intervention (n = 86). GC uptake was 67% in controls and 71% in the intervention group (P = 0.23). After adjusting for predefined variables and covariates, there was still no significant difference between groups (OR: 1.24, CI: 0.79–1.95, P = 0.34). Distant relatives had lower uptake than first-degree relatives (OR: 0.27, CI: 0.18–0.40, P < 0.001), while female relatives had higher uptake than males (OR: 2.17, CI: 1.50–3.12, P < 0.001). This is the largest RCT so far investigating direct letters to relatives. GC uptake was high in both groups, and the intervention of direct letters did not show superiority over family-mediated communication alone. Direct letters to relatives may complement family-mediated disclosure in certain situations, but should not be implemented as a general procedure in cancer genetics practices.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 10","pages":"1359-1367"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01922-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759562","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

“It’s a Godsend”: Parental experiences of genomic testing for paediatric inborn errors of immunity “这是天赐之物”：父母对儿童先天性免疫缺陷的基因组检测经验。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-29 DOI: 10.1038/s41431-025-01917-7

Amy Clark, Emily DeBortoli, Marisa Blancoe, Christopher Sgro, Tenielle Clinch, Mariana Melo, Alberto Pinzon-Charry, Anna Sullivan, Aideen McInerney-Leo, Jane Peake, Peter McNaughton, Tatiane Yanes

{"title":"“It’s a Godsend”: Parental experiences of genomic testing for paediatric inborn errors of immunity","authors":"Amy Clark, Emily DeBortoli, Marisa Blancoe, Christopher Sgro, Tenielle Clinch, Mariana Melo, Alberto Pinzon-Charry, Anna Sullivan, Aideen McInerney-Leo, Jane Peake, Peter McNaughton, Tatiane Yanes","doi":"10.1038/s41431-025-01917-7","DOIUrl":"10.1038/s41431-025-01917-7","url":null,"abstract":"Genomic testing has become essential to diagnosing and managing paediatric inborn errors of immunity (IEI), necessitating the development of mainstream models of care to facilitate optimal delivery of testing. However, little is known about the experiences of families undergoing paediatric IEI genomic testing within mainstream settings and parental experiences with such conditions remain underexplored. Thus, this study aimed to describe the experiences of parents of children who underwent mainstreamed IEI genomic testing. Semi-structured interviews were conducted with 17 parents (14 mothers and 3 fathers) of children with an IEI and thematically analysed. Six themes captured (i) the diverse dimensions of distress related to paediatric IEI, (ii) the associated social, practical and financial implications, (iii) the involvement of children in their care, (iv) parental satisfaction with mainstreamed genomic testing, (v) the value of multidisciplinary care, and (vi) considerations surrounding genomic testing decision-making. Findings highlight the significant psychosocial impacts of paediatric IEI, including distinct social and emotional challenges. High satisfaction with mainstreamed IEI genomic testing was reported by all parents. Recommendations for improvement include developing tailored resources to address families ongoing psychoeducational needs, enhancing mental health support, and involving children appropriately. Collectively, these findings substantiate the benefits of mainstreamed IEI genomic testing, while expanding literature on the psychosocial impact of such paediatric conditions. Further exploration of families and children’s needs and development of tailored resources are essential to ensure the delivery of patient-centred care.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 10","pages":"1342-1349"},"PeriodicalIF":4.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01917-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741724","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