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

Welcome to 2025 from EJHG 欢迎来到EJHG的2025年

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-01-08 DOI: 10.1038/s41431-024-01777-7

Alisdair McNeill

引用次数: 0

Predicting the phenotype of Pompe Disease from features of GAA variants. 从GAA变异的特征预测庞贝病的表型。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-01-07 DOI: 10.1038/s41431-024-01771-z

Geetanjali Rajamani, Nishitha R Pillai, Seth A Stafki, Peter I Karachunski, Peter B Kang

引用次数: 0

Double trouble: a comprehensive study into unrelated genetic comorbidities in adult patients with Facioscapulohumeral Muscular Dystrophy Type I. 双重麻烦：一项关于I型面肩肱肌营养不良症成人患者不相关遗传合并症的综合研究。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-01-07 DOI: 10.1038/s41431-024-01770-0

Angela Puma, Giulia Tammam, Andra Ezaru, Abderhmane Slioui, Eleonora Torchia, Giorgio Tasca, Luisa Villa, Michele Cavalli, Leonardo Salviati, Patrick J van der Vliet, Richard Jlf Lemmers, Jonathan Pini, Silvère M van der Maarel, Sabrina Sacconi

{"title":"Double trouble: a comprehensive study into unrelated genetic comorbidities in adult patients with Facioscapulohumeral Muscular Dystrophy Type I.","authors":"Angela Puma, Giulia Tammam, Andra Ezaru, Abderhmane Slioui, Eleonora Torchia, Giorgio Tasca, Luisa Villa, Michele Cavalli, Leonardo Salviati, Patrick J van der Vliet, Richard Jlf Lemmers, Jonathan Pini, Silvère M van der Maarel, Sabrina Sacconi","doi":"10.1038/s41431-024-01770-0","DOIUrl":"https://doi.org/10.1038/s41431-024-01770-0","url":null,"abstract":"Facioscapulohumeral dystrophy type 1 (FSHD1) displays prominent intra- and interfamilial variability, which complicates the phenotype-genotype correlation. In this retrospective study, we investigated FSHD1 patients classified as category D according to the Comprehensive Clinical Evaluation Form (CCEF), a category defined by FSHD patients showing uncommon clinical features, to identify genetic causes explaining these uncommon phenotypes. Demographics, clinical data and clinical scales of FSHD1 patients were retrospectively evaluated. Patients were divided into four CCEF categories, and comparisons between groups were performed. In category D, when uncommon features suggested the presence of an unrelated genetic disease, a more extensive collection of data was performed. 157 FSHD1 patients were included in the study (82 males, 75 females) with mean age of 52.1 ± 13.5 years at the time of the study. D4Z4 repeat sizes ranged between 2 and 10 RU. According to the CCEF, 114 patients were classified into category A, 8 into category B and C each, and 27 into category D. In category D, 9 patients presented uncommon features related to commonly acquired comorbidities, whereas in the remaining 18 patients, all but two with upper-sized FSHD1 D4Z4 repeats (7-10 RU), we suspected an unrelated genetic neurological disease based on clinical phenotype. In 14/18 patients, we identified FSHD-unrelated genetic causes, most often unrelated repeat expansion disorders. This emphasizes the need of careful clinical and genetic work-up to avoid confusion between FSHD-intrinsic clinical variability and clinical features unrelated to the disease.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947033","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

Characterisation of heritable TP53-related cancer syndrome in Sweden-a nationwide study of genotype-phenotype correlations in 90 families. 瑞典遗传性tp53相关癌症综合征的特征——对90个家庭基因型-表型相关性的全国性研究

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-01-05 DOI: 10.1038/s41431-024-01753-1

Meis Omran, Yaxuan Liu, Alexander Sun Zhang, Anna Poluha, Marie Stenmark-Askmalm, Fredrik Persson, Anna-Lotta Hallbeck, Anna Rosén, Hafdis T Helgadottir, Emma Tham, Svetlana Bajalica-Lagercrantz

{"title":"Characterisation of heritable TP53-related cancer syndrome in Sweden-a nationwide study of genotype-phenotype correlations in 90 families.","authors":"Meis Omran, Yaxuan Liu, Alexander Sun Zhang, Anna Poluha, Marie Stenmark-Askmalm, Fredrik Persson, Anna-Lotta Hallbeck, Anna Rosén, Hafdis T Helgadottir, Emma Tham, Svetlana Bajalica-Lagercrantz","doi":"10.1038/s41431-024-01753-1","DOIUrl":"https://doi.org/10.1038/s41431-024-01753-1","url":null,"abstract":"We aimed to describe the clinical characteristics of families with heritable TP53-related cancer (hTP53rc) syndrome in Sweden with class 4 and 5 germline TP53 variants (gTP53), and to evaluate the genotype-phenotype correlation. These results were also used to evaluate our previously published phenotype prediction model based on TP53 missense variants and their impact on protein conformation. 90 families with hTP53rc were initially identified in Sweden. After variant reclassification using the TP53-specific ACMG criteria, 83 families remained (176 carriers) to harbour a pathogenic (class 5) or likely pathogenic (class 4) variant in TP53. Of these, 112 carriers (64%) had a previous history of cancer, and 35 (31%) had developed more than one primary tumour. 16% of the families met the stricter criteria for Classic Li-Fraumeni syndrome, 45% the updated Chompret criteria, 35% for hereditary breast cancer (HBC), and the remaining 5% were classified as \"Others\". We identified 42 different gTP53 variants of which 22 were missense. The most frequently observed variant was the missense c.542 G > A, p.R181H identified in 14/29 (48%) of HBC families. Fifteen of the 20 informative missense variants (75%) were phenotypically predicted correctly using our previously published in silico prediction model. The TP53 p.R181H was identified as a common Swedish variant predominantly associated with an HBC phenotype. Apart from this variant, there were no significant genotype-phenotype correlations. Therefore, due to phenotypic overlap it is still too early to stratify surveillance programme for different TP53-carriers.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931093","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

Experiences of perinatal genetic screening for people from migrant and refugee backgrounds: a scoping review. 移民和难民背景人群围产期遗传筛查的经验：范围综述。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-01-04 DOI: 10.1038/s41431-024-01748-y

Anaita Kanga-Parabia, Alison D Archibald, Laura J Biggs, Sharon Lewis, Erin Tutty, Belinda Dawson-McClaren

{"title":"Experiences of perinatal genetic screening for people from migrant and refugee backgrounds: a scoping review.","authors":"Anaita Kanga-Parabia, Alison D Archibald, Laura J Biggs, Sharon Lewis, Erin Tutty, Belinda Dawson-McClaren","doi":"10.1038/s41431-024-01748-y","DOIUrl":"https://doi.org/10.1038/s41431-024-01748-y","url":null,"abstract":"People from refugee and migrant backgrounds often face poor experiences and outcomes in healthcare, and genetic healthcare is no exception. Understanding whether and how these health inequities manifest is an important step towards equitable perinatal genetic screening for genetic or chromosomal conditions (offered preconception, prenatally, or during the newborn period). A scoping review was conducted to review international evidence of perceptions and experiences of perinatal genetic screening for people from migrant and refugee backgrounds. Search strategies were applied to Medline, Embase, and CINAHL databases to identify articles meeting eligibility criteria. Evidence was synthesised using descriptive and content analysis, with theoretical frameworks of proportionate universality and relational autonomy used to interpret findings. Of 11,046 unique articles identified, twenty-six met inclusion criteria and underwent full-text review. Most studies were set in Western countries, and participants were primarily born in Asia, South America, or Africa. Studies indicated varying awareness, knowledge, attitudes, and uptake of screening. Several studies highlighted a lack of adequate in-language resources, the use of concepts that were unrecognised in particular communities, and poor interactions with healthcare providers. Strategies to address the above issues included person-centred counselling, increased consultation time, access to interpreters, and training for relevant providers. Other recommendations included addressing structural, financial, and geographical barriers to improve access to screening and associated care. Whilst additional research is required, we propose evidence and theory-informed strategies to improve perinatal genetic screening services for people from migrant and refugee backgrounds.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926879","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

C19orf12 gene variants causing mitochondrial membrane protein-associated neurodegeneration (MPAN). C19orf12基因变异引起线粒体膜蛋白相关神经变性（MPAN）。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-01-04 DOI: 10.1038/s41431-024-01778-6

Riyanka Kumari, Vikram V Holla, Neeharika Sriram, Nitish Kamble, Ajay Asranna, Jitender Saini, Gautham Arunachal, Ravi Yadav, Akhilesh Pandey, Pramod Kumar Pal, Babylakshmi Muthusamy

{"title":"C19orf12 gene variants causing mitochondrial membrane protein-associated neurodegeneration (MPAN).","authors":"Riyanka Kumari, Vikram V Holla, Neeharika Sriram, Nitish Kamble, Ajay Asranna, Jitender Saini, Gautham Arunachal, Ravi Yadav, Akhilesh Pandey, Pramod Kumar Pal, Babylakshmi Muthusamy","doi":"10.1038/s41431-024-01778-6","DOIUrl":"https://doi.org/10.1038/s41431-024-01778-6","url":null,"abstract":"Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare neurodegenerative disorder characterized by spastic paraplegia, parkinsonism and psychiatric and/or behavioral symptoms caused by variants in gene encoding chromosome-19 open reading frame-12 (C19orf12). We present here seven patients from six unrelated families with detailed clinical, radiological, and genetic investigations. Childhood-onset patients predominantly had a spastic ataxic phenotype with optic atrophy, while adult-onset patients were presented with cognitive, behavioral, and parkinsonian symptoms. Levodopa induced choreiform dyskinesia was observed in one patient who showed a response to levodopa. Brain magnetic resonance imaging showed mineralization in all patients and cerebellar atrophy in one patient. The \"pallidal splitting sign\" was found in two patients and additional caudate and putamen mineralization was noted in two patients. Exome sequencing identified six variants in the C19orf12 gene, including two novel splice-site variants, four previously reported missense variants. Transcript analysis using RT-PCR followed by Sanger sequencing was performed on a splice site variant (c.194-2delA) to understand the splice defect and its consequences. This analysis confirmed the splice defect and use of an alternate cryptic splice site in the downstream exonic region. The variants identified in this study expand the spectrum of clinical and genetic knowledge on MPAN patients, highlighting the importance of genetic testing in the diagnosis and management of this disorder.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926876","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-geneticist champions are essential to the mainstreaming of genomic medicine. 非遗传学家对基因组医学的主流化至关重要。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-01-03 DOI: 10.1038/s41431-024-01780-y

Michael P Mackley, Emma Weisz, Robin Z Hayeems, Clara Gaff, Belinda Dawson-McClaren

引用次数: 0

A tiered strategy to identify relevant genetic variants in familial pulmonary fibrosis: a proof of concept for the clinical practice. 鉴定家族性肺纤维化相关遗传变异的分层策略：临床实践的概念证明。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-01-02 DOI: 10.1038/s41431-024-01772-y

Aitana Alonso-González, Ibrahim Véliz-Flores, Eva Tosco-Herrera, Silvia González-Barbuzano, Alejandro Mendoza-Alvarez, Helena Galván-Fernández, Leandro Sastre, Beatriz Fernández-Varas, Almudena Corrales, Luis A Rubio-Rodríguez, David Jáspez, José M Lorenzo-Salazar, Maria Molina-Molina, Felipe Rodríguez-de-Castro, Rafaela González-Montelongo, Carlos Flores

{"title":"A tiered strategy to identify relevant genetic variants in familial pulmonary fibrosis: a proof of concept for the clinical practice.","authors":"Aitana Alonso-González, Ibrahim Véliz-Flores, Eva Tosco-Herrera, Silvia González-Barbuzano, Alejandro Mendoza-Alvarez, Helena Galván-Fernández, Leandro Sastre, Beatriz Fernández-Varas, Almudena Corrales, Luis A Rubio-Rodríguez, David Jáspez, José M Lorenzo-Salazar, Maria Molina-Molina, Felipe Rodríguez-de-Castro, Rafaela González-Montelongo, Carlos Flores","doi":"10.1038/s41431-024-01772-y","DOIUrl":"10.1038/s41431-024-01772-y","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a progressive, late-onset disease marked by lung scarring and irreversible loss of lung function. Genetic factors significantly contribute to both familial and sporadic cases, yet there are scarce evidence-based studies highlighting the benefits of integrating genetics into the management of IPF patients. In this study, we performed whole-exome sequencing and telomere length (TL) measurements on IPF patients and their relatives. We then identified rare deleterious variants using three virtual gene panels encompassing IPF or TL genes with varying levels of evidence supporting their potential relationship with the disease. We identified 10 candidate variants in well-established disease genes, and these results were validated using two automatic prioritization tools (Exomiser and Franklin). Pathogenic variants were found in two telomere-related genes (RTEL1 and NAF1), and both were associated with severe TL shortening. Our results suggest that this tiered virtual panel strategy is sufficiently robust and serves as a viable solution in clinical practice. It generates valuable genetic data which can be interpreted and validated with the expertise of a multidisciplinary team.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921257","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

RICTOR variants are associated with neurodevelopmental disorders. RICTOR变异与神经发育障碍有关。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2024-12-30 DOI: 10.1038/s41431-024-01774-w

Raphael Carapito, Anne Molitor, Lisa Pavinato, Alaa Skeyni, Magalie Lambert, Angélique Pichot, Jiuhong Jiang, Perrine Spinnhirny, Lucie Zimmermann, Philippe Boucher, Clara W T Chung, Noha Elserafy, Edward M Blair, Dong Li, Bhoj Elisabeth, Urania Kotzaeridou, Stephanie Karch, Matias Wagner, Roelineke J Lunsing, Rolph Pfundt, Kym M Boycott, Ange-Line Bruel, Frédéric Tran Mau-Them, Sébastien Moutton, Valerio Conti, Davide Mei, Valentina Cetica, Renzo Guerrini, Theresa Brunet, Patrick Rump, Alessandro Mussa, Alfredo Brusco, Gabrielle Lemire, Bert B A de Vries, Zhichao Miao, Bertrand Isidor, Seiamak Bahram

{"title":"RICTOR variants are associated with neurodevelopmental disorders.","authors":"Raphael Carapito, Anne Molitor, Lisa Pavinato, Alaa Skeyni, Magalie Lambert, Angélique Pichot, Jiuhong Jiang, Perrine Spinnhirny, Lucie Zimmermann, Philippe Boucher, Clara W T Chung, Noha Elserafy, Edward M Blair, Dong Li, Bhoj Elisabeth, Urania Kotzaeridou, Stephanie Karch, Matias Wagner, Roelineke J Lunsing, Rolph Pfundt, Kym M Boycott, Ange-Line Bruel, Frédéric Tran Mau-Them, Sébastien Moutton, Valerio Conti, Davide Mei, Valentina Cetica, Renzo Guerrini, Theresa Brunet, Patrick Rump, Alessandro Mussa, Alfredo Brusco, Gabrielle Lemire, Bert B A de Vries, Zhichao Miao, Bertrand Isidor, Seiamak Bahram","doi":"10.1038/s41431-024-01774-w","DOIUrl":"https://doi.org/10.1038/s41431-024-01774-w","url":null,"abstract":"RICTOR is a key component of the mTORC2 signaling complex which is involved in the regulation of cell growth, proliferation and survival. RICTOR is highly expressed in neurons and is necessary for brain development. Here, we report eight unrelated patients presenting with intellectual disability and/or development delay and carrying variants in the RICTOR gene. The phenotypic presentation is diverse with associated features including growth failure, feeding difficulties, abnormal behavior, seizure, hypertonia, brain anomalies and various other congenital organ and skeletal malformations. All patients carried de novo or heterozygous variants inherited from one affected parent, including three missense variants, four loss-of-function variants and one 3 kb deletion encompassing RICTOR. The mTORC2 pathway was hyperactivated in a patient's fibroblasts carrying a missense variant, while the expression of RICTOR remained unchanged, indicating a gain-of-function mechanism. RNA sequencing on RICTOR knock-out mouse embryonic fibroblasts confirmed the potential role of RICTOR in neuronal cell development.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909520","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

Vascular Ehlers-Danlos syndrome in children: evaluating the importance of diagnosis and follow-up during childhood. 儿童血管性埃勒-丹洛斯综合征：评估儿童期诊断和随访的重要性。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2024-12-27 DOI: 10.1038/s41431-024-01773-x

Niamh R Wilkinson, Elena Cervi, Bart Wagner, Deborah Morris-Rosendahl, Duncan Baker, Harpaul Flora, Kate von Klemperer, Toby Andrew, Neeti Ghali, Fleur S van Dijk

{"title":"Vascular Ehlers-Danlos syndrome in children: evaluating the importance of diagnosis and follow-up during childhood.","authors":"Niamh R Wilkinson, Elena Cervi, Bart Wagner, Deborah Morris-Rosendahl, Duncan Baker, Harpaul Flora, Kate von Klemperer, Toby Andrew, Neeti Ghali, Fleur S van Dijk","doi":"10.1038/s41431-024-01773-x","DOIUrl":"https://doi.org/10.1038/s41431-024-01773-x","url":null,"abstract":"Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder predominantly caused by pathogenic COL3A1 variants. Characteristic arterial and intestinal fragility and generalised severe tissue friability can lead to clinical events from childhood. We highlight a paucity of literature regarding children diagnosed with vEDS, possibly explained by a restraint in predictive testing, and present data on 63 individuals (23 index cases) with a clinical and genetic diagnosis of vEDS in childhood (<18 years) to address this. Patients were identified through the National Ehlers-Danlos Syndrome (EDS) Service London. We report on 18 events in childhood, recorded in 13 individuals. First events occurred at a median age of 11 years (IQR 0-13) and genetic testing was initiated as a direct result of the first event in 11/13 cases. In the cohort majority, diagnosis was the result of familial genetic testing (55%). Our findings emphasise the importance of offering genetic testing in childhood when there is a positive family history of vEDS and/or features suggestive of a potential inherited connective tissue disorder. Diagnosis in childhood allows for follow-up surveillance and informed multi-disciplinary management, in addition to genetic counselling and patient-led management including lifestyle modification. As seen in adult cohorts, we anticipate children with vEDS will experience the same protective benefit afforded by early diagnosis and present preliminary data on follow-up in childhood. Formal evaluation of the impact that diagnosis of vEDS in childhood has on disease management is needed when sufficient data is internationally available.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893240","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