European Journal of Human Genetics最新文献

{"title":"A Spanish-Portuguese GWAS of progressive supranuclear palsy reveals a novel risk locus in NFASC","authors":"Pablo García-González, Héctor Rodrigo Lara, Yaroslau Compta, Manuel Fernandez, Sven J. van der Lee, Itziar de Rojas, Laura Saiz, Celia Painous, Ana Camara, Esteban Muñoz, Maria J. Marti, Francesc Valldeoriola, Raquel Puerta, Ignacio Illán-Gala, Javier Pagonabarraga, Oriol Dols-Icardo, Jaime Kulisevsky, Juan Fortea, Alberto Lleó, Claudia Olivé, Sterre C. M. de Boer, Marc Hulsman, Yolande A. L. Pijnenburg, Rafael Díaz Belloso, Laura Muñoz-Delgado, Dolores Buiza Rueda, Pilar Gómez-Garre, Iban Aldecoa, Gemma Aragonés, Jorge Hernandez Vara, Maite Mendioroz, Jordi Pérez-Tur, Pieter Jelle Visser, Anouk den Braber, Janne M. Papma, Ángel Martín Montes, Eloy Rodriguez-Rodriguez, Josep Blázquez-Folch, Andrea Miguel, Fernando García-Gutiérrez, Amanda Cano, Sergi Valero, Marta Marquié, María Capdevila-Bayo, Maitee Rosende-Roca, Inés Quintela, Ángel Carracedo, Lluís Tàrraga, Luis M. Real, Jose Luis Royo, María Elena Erro, Carmen Guerrero, Daniela Corte Torres, Marta Blázquez-Estrada, Beatriz San Millán, Susana Teijeira, Dolores Vilas Rolan, Isabel Hernández, Antonio Sánchez-Soblechero, Beatriz de la Casa-Fages, Soledad Serrano López, Raquel Baviera-Muñoz, Amaya Lavín, Ricardo Taipa, Guillermo Amer, Elena Martinez-Saez, Marta Fernández-Matarrubia, Carmen Lage-Martínez, Victoria Álvarez, Laura Molina-Porcel, Henne Holstege, Pablo Mir, Olivia Belbin, Mercè Boada, Victoria Fernández, María J. Bullido, Alberto Rábano, Pascual Sánchez-Juan, Agustín Ruiz","doi":"10.1038/s41431-025-01872-3","DOIUrl":"10.1038/s41431-025-01872-3","url":null,"abstract":"Progressive supranuclear palsy (PSP) is a rare 4-repeat tauopathy that causes behavioural, movement and cognitive abnormalities. We genotyped all available clinical and histopathological PSP cases in Spain and Portugal (N = 522), and conducted the largest PSP GWAS of the Iberian population to date. Genetic burden analysis revealed reduced diagnostic specificity in clinically diagnosed atypical PSP cases—when applying the 2017 MDS criteria—compared to Richardson’s syndrome cases. We independently replicated eight PSP risk variants in seven known loci (MAPT, MOBP, EIF2AK3, STX6, SLCO1A2, DUSP10 and APOE), and identified a novel locus in NFASC/CNTN2 (rs12744678 C: OR[95%CI] = 0.83[0.78–0.89]; p = 4.15·10−08) after meta-analysis with a newly available Dutch cohort and publicly available summary statistics (3,099 PSP; 11,482 controls). Enrichment analysis and protein expression profiling highlighted oligodendrocyte function and myelination as likely contributors to PSP pathogenesis. Our findings broaden the genetic landscape of PSP and suggest potential therapeutic avenues focused on modulating neuron–oligodendrocyte interactions.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 7","pages":"960-965"},"PeriodicalIF":3.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086136","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":"Understanding speech and language in KIF1A-associated neurological disorder.","authors":"Lottie D Morison, Adam P Vogel, John Christodoulou, Wendy A Gold, Dylan Verden, Wendy K Chung, Ruth Braden, Joanna Bredebusch, Simranpreet Kaur, Ingrid E Scheffer, Angela T Morgan","doi":"10.1038/s41431-025-01867-0","DOIUrl":"10.1038/s41431-025-01867-0","url":null,"abstract":"<p><p>KIF1A-associated neurological disorder (KAND) is a genetic condition characterised by motor, cognitive and ophthalmologic features. The speech and language phenotype have not been systematically analysed. Here, we assess speech and language using observer- and clinician-reported outcomes, and performance outcome measures. 44 individuals (25 female) with KAND (median age 7 years, range 1-60 years) participated. Median age at diagnosis was 4 years (range 0.5-58 years). KIF1A variants were missense (41/44 individuals, 93%), intragenic deletion (2/44, 5%) and splice site (1/44, 2%). Age at first words was delayed (>12 months) in 38/44 (86%) individuals. At assessment, 28/44 (64%) combined words into sentences and all of the 20 individuals assessed had dysarthria. Apraxic speech features and phonological impairments occurred in children aged under 8 years. 36/37 (97%) participants had language impairment, with expressive language skills stronger than receptive (p = 0.02) and written (p = 0.03) language on the Vineland Adaptive Behaviour Scales. 7/32 (22%) caregivers reported speech and language regression. Mild to severe intellectual disability occurred in 31/33 (94%) individuals. 22/44 (50%) participants had used augmentative and alternative communication, such as key word sign or speech generating devices. Individuals had average social motivation skills in contrast to moderately impaired social cognition, communication and awareness on the Social Responsiveness Scale (p < 0.05). 16/44 (36%) had epilepsy and 40/44 (91%) had visual impairment, namely nystagmus (16/44, 36%), optic nerve atrophy and strabismus (both 12/44, 27%). Individuals with KAND frequently have speech and language disorders necessitating early and targeted speech and language interventions.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086138","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":"Recessive variants in WSB2 encoding a substrate receptor of E3 ubiquitin ligase underlie a neurodevelopmental syndrome.","authors":"Shiyu Luo, Valérie Gailus-Durner, Bobbi McGivern, Qifei Li, Jessica Kottmeier, Mai-Lan Ho, Hagar Mor-Shaked, Orly Elpeleg, Erfan Aref-Eshghi, Amanda C Brodeur, Klaus Schmitz-Abe, Casie A Genetti, Jonathan Picker, Jiahai Shi, Reem Ibrahim Bux, Tawfeg Ben-Omran, Helmut Fuchs, Tamar Harel, Martin Hrabě de Angelis, Pankaj B Agrawal","doi":"10.1038/s41431-025-01863-4","DOIUrl":"https://doi.org/10.1038/s41431-025-01863-4","url":null,"abstract":"<p><p>WD40 and SOCS box protein-2 (WSB2), a member of the large family of suppressor of cytokine signaling (SOCS)-box proteins, has recently been identified as a substrate receptor of cullin 5 E3 ligase that plays an important role in proteomic regulation through substrate ubiquitination and proteasomal degradation. Here we report five patients from four unrelated families presenting with neurodevelopmental delay, dysmorphic features, brain structural abnormalities with or without growth restriction, hypotonia, and microcephaly, all of whom are homozygous for extremely rare and predicted loss-of-function (pLoF) or missense variants in WSB2, inherited from consanguineous parents. The Wsb2-mutant mice exhibited several neurological findings that included hyperactivity, altered exploration, and hyper alertness. They also weighed less, had a lower heart rate, and presented an abnormal retinal blood vessel morphology and vasculature pattern along with decreased total thickness of the retina. Our findings suggest that homozygous LoF WSB2 variants cause a novel neurodevelopmental disorder in humans with similar neurologic and developmental findings seen in Wsb2-mutant mouse models.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208090","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":"Cell-type specific global reprogramming of the transcriptome and epigenome in induced neurons with the 16p11.2 neuropsychiatric CNVs.","authors":"Thomas R Ward, Ping-Ping Qu, Louis C Leung, Bo Zhou, Kristin L Muench, Arineh Khechaduri, Melanie J Plastini, Carol A Charlton, Reenal Pattni, Steve Ho, Marcus Ho, Yiling Huang, Patrick Zhou, Joachim F Hallmayer, Philippe Mourrain, Theo D Palmer, Xianglong Zhang, Alexander E Urban","doi":"10.1038/s41431-025-01856-3","DOIUrl":"10.1038/s41431-025-01856-3","url":null,"abstract":"<p><p>Copy number variants (CNVs), either deletions or duplications, at the 16p11.2 locus in the human genome are known to increase the risk for autism spectrum disorders (ASD), schizophrenia, and several other developmental conditions. Here, we investigate the global effects on gene expression and DNA methylation using an induced pluripotent stem cell (iPSC) to induced neuron (iN) cell model system derived from 16p11.2 CNV patients and controls. This approach revealed genome-wide and cell-type specific alterations to both gene expression and DNA methylation patterns and also yielded specific leads on genes potentially contributing to some of the phenotypes in 16p11.2 patients. There is global reprogramming of both the transcriptome and the DNA methylome. We observe sets of differentially expressed genes and differentially methylated regions, respectively, that are localized genome wide and that are shared, and with changes in the same direction, between the deletion and duplication genotypes. The gene PCSK9 is identified as a possible contributing factor to symptoms seen in carriers of the 16p11.2 CNVs. The protocadherin (PCDH) gene family is found to have altered DNA methylation patterns in the CNV patient samples. The iPSC lines used for this study are available through a repository as a resource for research into the molecular etiology of the clinical phenotypes of 16p11.2 CNVs and into that of neuropsychiatric and neurodevelopmental disorders in general.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076714","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":"Further delineation of defects in MRPS2 causing human OXPHOS deficiency and early developmental abnormalities in zebrafish.","authors":"Amoolya Kandettu, Mayuri Yeole, Hamsini Sekar, Kishore Garapati, Namanpreet Kaur, Aakanksha Anand, Pranavi Hegde, Karthik Nair, Raghavender Medishetti, Vivekananda Bhat, Periyasamy Radhakrishnan, Suneel C Mundkur, Hebbar A Shrikiran, Akhilesh Pandey, Aarti Sevilimedu, Sanjiban Chakrabarty, Anju Shukla","doi":"10.1038/s41431-025-01858-1","DOIUrl":"https://doi.org/10.1038/s41431-025-01858-1","url":null,"abstract":"<p><p>Mitochondrial ribosomal protein-small 2 (MRPS2) encodes a vital structural protein essential for assembling mitoribosomal small subunit and thus mitochondrial translation. Any defect in mitochondrial translation impacts OXPHOS activity and cellular respiration. Defects in MRPS2 have been implicated recently in four families with combined oxidative phosphorylation deficiency-36 (MIM# 617950). We herein describe two individuals from two unrelated families with variable phenotypes of acute onset severe metabolic decompensation and symptomatic hypoglycemia. Exome sequencing identified bi-allelic variants in MRPS2 (NM_016034.5) in the affected individuals: P1: c.490 G > A p.(Glu164Lys); and P2: c.413 G > A p.(Arg138His). Further evaluation of the variant c.490 G > A p.(Glu164Lys) in patient-derived skin fibroblasts revealed decreased expression of MRPS2 transcript and protein levels of MRPS2 along with expression of complex I and IV proteins. Proteomics analysis revealed decreased expression of small subunit proteins and increased expression of large subunit proteins. Also, reduced complex I and IV enzyme activities, mitochondrial respiration (OCR), and altered mitochondrial morphology on confocal imaging were observed. Additionally, mrps2 knockout zebrafish larvae demonstrated an abnormal developmental phenotype and reduced Complex IV activity. With these findings, we identify additional families with variants in MRPS2, illustrating the variable clinical spectrum and validate the pathogenicity of defects in MRPS2 through in-vitro and in-vivo assays.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984378","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":"Townes-Brocks syndrome: genotype-phenotype correlations of SALL1 variants in our series and the literature.","authors":"Fiona Leduc, Perrine Brunelle, Fabienne Escande, Nassima Ramdane, Laurence Bellengier, Léa Giacomello, Christine Lefevre, Aurélie Mezel, Charlotte Samaille, Rony Sfeir, Philippine Toulemonde, Sylvie Manouvrier-Hanu, Catherine Vincent-Delorme, Florence Petit, Clémence Vanlerberghe","doi":"10.1038/s41431-025-01855-4","DOIUrl":"https://doi.org/10.1038/s41431-025-01855-4","url":null,"abstract":"<p><p>Townes-Brocks syndrome (TBS, MIM#107480) is an autosomal dominant disorder linked to SALL1 alterations and characterized by a clinical triad (anorectal, thumb, and external-ear malformations), along with variable features. Renal failure and deafness can occur at any age, making follow-up essential. Some genotype-phenotype correlations have been suggested but data are limited. We collected clinical and molecular data from 49 patients with a SALL1 (likely) pathogenic variant identified in our laboratory or through collaborations, and reviewed the 207 SALL1 related-TBS patients previously reported in the literature. We performed statistical analysis to study genotype-phenotype correlations based notably on the variant position in relation to the glutamine-rich region. In our series, 25% of individuals presented with the clinical triad compared to 49.7% in the literature. The deafness frequency was similar (65%). Renal failure was diagnosed in 39.6% of our patients compared to 29.3% in the literature. Developmental delay or intellectual disability affected 9% of patients. Of the 22 SALL1 variants in our series, 35% were located upstream of the glutamine-rich region, compared to 6.5% in the literature. Statistical analysis was performed on all patients, of which 26 and 200 carried a variant upstream and downstream of the glutamine-rich region, respectively. A significant increase in deafness, dysplastic ear, and thumb malformations and a significant decrease in renal failure were observed in the individuals carrying a variant located downstream of the region, but the patients were significantly younger. Future studies should aim to elucidate the complex pathophysiological mechanisms and prognosis of TBS, functionally and prospectively.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976451","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":"Modifier variants in metabolic pathways are associated with an increased penetrance of Leber's Hereditary Optic Neuropathy.","authors":"Eszter Sara Arany, Catarina Olimpio, Ida Paramonov, Rita Horvath","doi":"10.1038/s41431-025-01860-7","DOIUrl":"https://doi.org/10.1038/s41431-025-01860-7","url":null,"abstract":"<p><p>Leber's hereditary optic neuropathy (LHON) is a debilitating mitochondrial disease characterised by bilateral painless vision loss. Despite being the most prevalent mitochondrial disorder, the precise pathophysiological mechanisms underlying the penetrance of LHON remain poorly understood. Nuclear modifier genes have been long suspected to affect phenotype-severity, however, specific cellular pathways implicated in the disease penetrance have been only suggested recently. In recent years, autosomal recessive variants in nuclear genes involved in complex I function and metabolic pathways were recognised to cause a typical LHON phenotype. This was proposed as a new autosomal recessive disease mechanism for LHON (arLHON). The association between nuclear variants and the LHON phenotype makes the nuclear pathways disrupted in arLHON the strongest candidates to act as modifiers of mitochondrial LHON (mLHON). In this study we systematically investigated a large cohort of 23 symptomatic and 28 asymptomatic individuals carrying one of the three primary mitochondrial LHON variants. We identified several heterozygous pathogenic nuclear variants amongst the affected individuals that were consistently linked to metabolic and complex I related pathways, mirroring those disrupted in arLHON. Our findings are consistent with the presence of a second hit in specific biological pathways impairing ATP production. We propose that in addition to the primary mitochondrial variants, disruption in these nuclear-encoded pathways drives the clinical manifestation of LHON. Genes involved in the same pathways also emerge as exciting candidates for future association with arLHON. The present study deepens our understanding of LHON's pathophysiology and provides a new framework for identifying novel disease-modifying targets.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976449","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":"UYSD: a novel data repository accessible via public website for worldwide population frequencies of Y-SNP haplogroups","authors":"Arwin Ralf,&nbsp;Dion Zandstra,&nbsp;Bram van Wersch,&nbsp;Zehra Köksal,&nbsp;Maarten H. D. Larmuseau,&nbsp;Alexandra Rosa,&nbsp;Mark A. Jobling,&nbsp;Maria E. D’Amato,&nbsp;Cornelius Courts,&nbsp;Mario Gysi,&nbsp;Cordula Haas,&nbsp;Rodrigo Flores,&nbsp;Maximilian Neis,&nbsp;Jon H. Wetton,&nbsp;Kevin Kiesler,&nbsp;Adam Ameur,&nbsp;Simon Azonbakin,&nbsp;Alexandra Bôžiková,&nbsp;Andrej Choma,&nbsp;Maria Corazon De Ungria,&nbsp;Beatrice Corradini,&nbsp;Catarina Cruz,&nbsp;Bettina Dunkelmann,&nbsp;Gianmarco Ferri,&nbsp;Jan Fleckhaus,&nbsp;Domniki Fragou,&nbsp;Noah Gaens,&nbsp;Rita Gonçalves,&nbsp;Dubravka Havaš Auguštin,&nbsp;Katharina Helm,&nbsp;Petra Hölzl-Müller,&nbsp;Michał Kaliszan,&nbsp;Mohaimin Kasu,&nbsp;Leda Kovatsi,&nbsp;Mpasi Lesaoana,&nbsp;Natsuko Mizuno,&nbsp;Franz Neuhuber,&nbsp;Jana Nováčková,&nbsp;Alena Ňuňuková,&nbsp;Horolma Pamjav,&nbsp;Walther Parson,&nbsp;Yerlan Ramankulov,&nbsp;Héctor Rangel Villalobos,&nbsp;Krzysztof Rębała,&nbsp;Siiri Rootsi,&nbsp;Jazelyn Salvador,&nbsp;Jelena Šarac,&nbsp;Carolyn R. Steffen,&nbsp;Vlastimil Stenzl,&nbsp;Tibor Török,&nbsp;Richard Villems,&nbsp;Haruhiko Watahiki,&nbsp;Maxat Zhabagin,&nbsp;Peter M. Schneider,&nbsp;Manfred Kayser","doi":"10.1038/s41431-025-01854-5","DOIUrl":"10.1038/s41431-025-01854-5","url":null,"abstract":"For decades, there has been scientific interest in the variation and geographic distribution of paternal lineages associated with the human Y chromosome. However, the relevant data have been dispersed across numerous publications, making it difficult to consolidate. Additionally, understanding the relationships between different variants, and the tools used to analyze them, have evolved over time, further complicating efforts to harmonize this information. The Universal Y-SNP Database (UYSD) marks a substantial advancement by providing a comprehensive and accessible platform for Y-SNP and haplogroup data from populations around the world. UYSD harmonizes diverse datasets into a unified repository, facilitating the exploration of global Y-chromosomal variation. The platform handles data generated with both high- and low-throughput technology and is compatible with the automated analysis software tool, Yleaf v3. Key functionalities include the ability to: i) visualize haplogroup distributions on an interactive world map, ii) estimate haplogroup frequencies in geographic regions with sparse data through interpolation, and iii) display detailed phylogenetic trees of Y-chromosomal haplogroups. Currently, UYSD encompasses data from over 6,600 males across 27 populations. This dataset largely aligns with known global Y-haplogroup patterns, but also reveals unexplored finer-scale geographic variations. While the present dataset is largely European-centered, UYSD is designed for ongoing expansion by the scientific community, aiming to include more global data and higher-resolution population sequencing data. The platform thus offers valuable insights into human genetic diversity and migration patterns, serving several fields of research such as: human population genetics, genetic anthropology, ancient DNA analysis and forensic genetics.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 7","pages":"904-912"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41431-025-01854-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980361","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":"Autistic perspectives on the moral and ethical considerations of genetic testing for autism","authors":"Mitch Hendry,&nbsp;Loryn Byres,&nbsp;Jehannine Austin","doi":"10.1038/s41431-025-01862-5","DOIUrl":"10.1038/s41431-025-01862-5","url":null,"abstract":"This study aimed to characterize the nuanced perspectives expressed by Autistic adults about genetic testing for autism. In this secondary analysis of an existing dataset, we used inductive content analysis of free-text responses that Autistic adults wrote in response to questions asking about perceptions of genetic testing for autism that had been included in a previous survey. Participants who completed the survey had been recruited online. Three-hundred eighty-nine participants wrote a total of 28,774 words in response to the questions of interest. While some respondents wrote about potential benefits of genetic testing (79/389), more (333/389) wrote about potential negative outcomes of genetic testing. Participants wrote about concerns of eugenics (281/389), described a lack of trust in how genetics information would be used (125/389), and raised concerns that genetic testing could increase discrimination (66/389). This is the largest study to date to conduct an in-depth analysis of Autistic adults’ opinions on genetic testing for autism. Most respondents raised serious concerns. Additional work is needed to collect more Autistic opinions about genetic testing for autism.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 10","pages":"1316-1323"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004480","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":"Opportunities and challenges for paediatricians requesting funded genomic tests for children","authors":"Belinda Dawson-McClaren,&nbsp;Melissa Martyn,&nbsp;Jessica Ince,&nbsp;Alli Jan,&nbsp;Natasha J. Brown,&nbsp;Michael C. Fahey,&nbsp;Erin Crellin,&nbsp;Clara Gaff","doi":"10.1038/s41431-025-01864-3","DOIUrl":"10.1038/s41431-025-01864-3","url":null,"abstract":"Genomic diagnosis for children with childhood syndromes can inform treatment, management and reproductive planning. Shortages in the clinical genetics workforce mean that practices are changing, with paediatricians likely requesting initial genomic investigations and clinical genetics services reserved for particularly complex cases or post-test genetic counselling. In Australia, paediatricians can request funded genomic testing for patients, yet ordering rates are less than a quarter predicted. Using a theory-informed approach, we aimed to understand barriers and enablers to general paediatricians’ practice as the essential first step in developing complex interventions to support clinical practice. Maximum variation sampling was used to invite general paediatricians to complete a semi-structured interview. The interview guide used a process map of the steps involved in ordering funded genomic tests, with questions addressing the components of the Capability, Opportunity, Motivation – Behaviour (COM-B) model and the Theoretical Domains Framework. Twenty-six general paediatricians with diverse practice experience participated. Paediatricians described barriers related to capability, opportunity and motivation. Intuitive strategies general paediatricians suggested to overcome barriers aligned with theoretical strategies to implement practice change. These included: raising awareness using avenues paediatricians already access for clinical information; providing opportunities for experiential learning to build on foundational knowledge; having practical resources in one easily accessible location; family-friendly information materials to share with patients. This study provides evidence to inform a roadmap of strategies to effectively support general paediatricians in incorporating genomics into their practice and ultimately delivering faster, more equitable genomic medicine.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 9","pages":"1173-1179"},"PeriodicalIF":4.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01864-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986785","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}