Journal of Medical Genetics最新文献

{"title":"Complex structural variation and nonsense variant <i>in trans</i> cause <i>VPS50</i>-related disorder.","authors":"Laura Hecher, Esther Gorski-Alberts, Matthias Begemann, Johanna Herwig, Eva Lausberg, Georg Hillebrand, Alexander E Volk, Ingo Kurth, Florian Kraft, Kerstin Kutsche","doi":"10.1136/jmg-2024-109983","DOIUrl":"10.1136/jmg-2024-109983","url":null,"abstract":"<p><p>Homozygous <i>VPS50</i> variants have been previously described in two unrelated patients with a neurodevelopmental disorder with microcephaly, seizures and neonatal cholestasis. <i>VPS50</i> encodes a subunit that is unique to the heterotetrameric endosome-associated recycling protein (EARP) complex. The other subunits of the EARP complex, such as VPS51, VPS52 and VPS53, are also shared by the Golgi-associated retrograde protein complex. We report on an 18-month-old female patient with biallelic <i>VPS50</i> variants. She carried a paternally inherited heterozygous nonsense c.13A>T; p.(Lys5*) variant. By long-read genome sequencing, we characterised a structural variant with a 4.3 Mb inversion flanked by deletions at both breakpoints on the maternal allele. The ~428 kb deletion at the telomeric inversion breakpoint encompasses the entire <i>VPS50</i> gene. We demonstrated a deficiency of VPS50 in patient-derived fibroblasts, confirming the loss-of-function nature of both <i>VPS50</i> variants. VPS53 and VPS52 protein levels were significantly reduced and absent, respectively, in fibroblasts of the patient. These data show that VPS50 and/or EARP deficiency and the associated functional defects underlie the phenotype in patients with <i>VPS50</i> pathogenic variants. The <i>VPS50</i>-related core phenotype comprises severe developmental delay, postnatal microcephaly, hypoplastic corpus callosum, neonatal low gamma-glutamyl transpeptidase cholestasis and failure to thrive. The disease is potentially fatal in early childhood.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"833-838"},"PeriodicalIF":3.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>IFIH1</i> variants are associated with generalised epilepsy preceded by febrile seizures.","authors":"Wang Song, Wen-Jun Bian, Hua Li, Qing-Hui Guo, Jie Wang, Bin Tang, Jia-Yuan Zhang, Wei Wei, Xiao-Rong Liu, Wei-Ping Liao, Bin Li, Na He","doi":"10.1136/jmg-2024-109950","DOIUrl":"10.1136/jmg-2024-109950","url":null,"abstract":"<p><strong>Background: </strong><i>IFIH1</i> variants have been reported to be associated with immune-related disorders with/without seizures. It is unknown whether <i>IFIH1</i> variants are associated with common epilepsy without acquired causes and the mechanism underlying phenotypic variation remains elusive.</p><p><strong>Methods: </strong>Trio-based whole-exome sequencing was performed on patients with febrile seizures or epilepsy with antecedent febrile seizures. Previously reported variants were systematically reviewed to investigate genotype-phenotype associations.</p><p><strong>Results: </strong>Two de novo heterozygous and three biallelic missense variants were identified in five patients with generalised epilepsy with antecedent febrile seizures. The variants were predicted to be damaging by in silico tools and were associated with hydrogen bonding changes to neighbouring amino acids or decreased protein stability. Patients exhibited an early onset age and became seizure-free with favourable outcome. Further analysis revealed that de novo missense variants located in the Hel region resulted in seizures with multiple neurological abnormalities, while those in the pincer domain or C-terminal domain led to seizures with normal neurodevelopment, suggesting a sub-molecular effect. Biallelic missense variants, which were inherited from unaffected parents and presented low allele frequencies in general populations, were associated with seizures without neurological abnormalities. Truncation variants were related to refractory epilepsy and severe developmental delay, suggesting a genotype-phenotype correlation. <i>IFIH1</i> is predominantly expressed in the neonatal stage and decreases dramatically in the adulthood, which is consistent with the early onset age and favourable outcome of the patients.</p><p><strong>Conclusions: </strong><i>IFIH1</i> variants are potentially associated with generalised epilepsy with antecedent febrile seizures. The sub-molecular implication and genotype-phenotype association help explain phenotype variations of <i>IFIH1</i> variants.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"895-903"},"PeriodicalIF":3.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating cancer risk in carriers of Lynch syndrome variants in UK Biobank.","authors":"Eilidh Fummey, Pau Navarro, John-Paul Plazzer, Ian M Frayling, Sara Knott, Albert Tenesa","doi":"10.1136/jmg-2023-109791","DOIUrl":"10.1136/jmg-2023-109791","url":null,"abstract":"<p><p>BackgroundLynch syndrome (LS) is an inherited cancer predisposition syndrome caused by genetic variants affecting DNA mismatch repair (MMR) genes <i>MLH1</i>, <i>MSH2</i>, <i>MSH6</i> and <i>PMS2</i> Cancer risk in LS is estimated from cohorts of individuals ascertained by individual or family history of cancer, which may upwardly bias estimates.</p><p><strong>Methods: </strong>830 carriers of pathogenic or likely pathogenic (<i>path_MMR</i>) MMR gene variants classified by InSiGHT were identified in 454 756 UK Biobank (UKB) participants using whole-exome sequence. Nelson-Aalen survival analysis was used to estimate cumulative incidence of colorectal, endometrial and breast cancer (BC).</p><p><strong>Results: </strong>Cumulative incidence of colorectal and endometrial cancer (EC) by age 70 years was elevated in <i>path_MMR</i> carriers compared with non-carriers (colorectal: 11.8% (95% confidence interval (CI): 9.5% to 14.6%) vs 1.7% (95% CI: 1.6% to 1.7%), endometrial: 13.4% (95% CI: 10.2% to 17.6%) vs 1.0% (95% CI: 0.9% to 1.0%)), but the magnitude of this increase differed between genes. Cumulative BC incidence by age 70 years was not elevated in <i>path_MMR</i> carriers compared with non-carriers (8.9% (95% CI: 6.3% to 12.4%) vs 7.5% (95% CI: 7.4% to 7.6%)). Cumulative cancer incidence estimates in UKB were similar to estimates from the Prospective Lynch Syndrome Database for all genes and cancers, except there was no evidence for elevated EC risk in carriers of pathogenic <i>PMS2</i> variants in UKB.</p><p><strong>Conclusion: </strong>These results support offering incidentally identified carriers of any <i>path_MMR</i> surveillance to manage colorectal cancer risk. Incidentally identified carriers of pathogenic variants in <i>MLH1</i>, <i>MSH2</i> and <i>MSH6</i> would also benefit from interventions to reduce EC risk. The results suggest that BC is not an LS-related cancer.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"861-869"},"PeriodicalIF":3.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>POT1</i> and multiple primary melanomas: the dermatological phenotype.","authors":"Ellie J Maas, Emily DeBortoli, Vaishnavi Nathan, Ned P Freeman, Adam Mothershaw, Darren J Smit, Brigid Betz-Stablein, Lauren G Aoude, Mitchell S Stark, Richard A Sturm, H Peter Soyer, Aideen M McInerney-Leo","doi":"10.1136/jmg-2023-109637","DOIUrl":"10.1136/jmg-2023-109637","url":null,"abstract":"<p><p><i>POT1</i> is the second most frequently reported gene (after <i>CDKN2A</i>) in familial melanoma. Pathogenic variants are associated with earlier onset and/or multiple primary melanomas (MPMs). To date, <i>POT1</i> phenotypical reports have been largely restricted to associated malignancies, and description of the dermatological landscape has been limited. We identified 10 variants in n=18 of 384 (4.7%) unrelated individuals (n=13 MPMs; n=5 single primary melanomas) of European ancestry. Five variants were rare (minor allele frequency <0.001) or novel (two loss-of-function (LOF), one splice acceptor and two missense) and were predicted to be functionally significant, in five unrelated probands with MPMs (≥3 melanomas). We performed three-dimensional total body photography on both individuals with confirmed pathogenic LOF variants to characterise the dermatological phenotype. Total body naevus counts (≥2 mm diameter) were significantly higher (p=7.72^×10-12) in carriers compared with a control population. Majority of naevi were on the probands' back and lower limb regions, where only mild to moderate ultraviolet (UV) damage was observed. Conversely, the head/neck region, where both probands exhibited severe UV damage, had comparably fewer naevi. We hypothesise that carriage of functionally significant <i>POT1</i> variants is associated with increased naevus counts generally, and naevi >5 mm in diameter specifically and the location of these are independent of UV damage.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"891-894"},"PeriodicalIF":3.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>JMG</i> at 60.","authors":"Huw Dorkins","doi":"10.1136/jmg-2024-110287","DOIUrl":"10.1136/jmg-2024-110287","url":null,"abstract":"","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"823"},"PeriodicalIF":3.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS): new insights from the fetal perspective.","authors":"Silvestre Cuinat, Chloé Quélin, Claire Effray, Christèle Dubourg, Gwenaelle Le Bouar, Anne-Sophie Cabaret-Dufour, Philippe Loget, Maia Proisy, Fanny Sauvestre, Mélie Sarreau, Sophie Martin-Berenguer, Claire Beneteau, Sophie Naudion, Vincent Michaud, Benoit Arveiler, Aurélien Trimouille, Pierre Macé, Sabine Sigaudy, Olga Glazunova, Julia Torrents, Laure Raymond, Marie-Hélène Saint-Frison, Tania Attié-Bitach, Mathilde Lefebvre, Yline Capri, Nicolas Bourgon, Christel Thauvin-Robinet, Frédéric Tran Mau-Them, Ange-Line Bruel, Antonio Vitobello, Anne-Sophie Denommé-Pichon, Laurence Faivre, Anne-Claire Brehin, Alice Goldenberg, Sophie Patrier-Sallebert, Alexandre Perani, Benjamin Dauriat, Sylvie Bourthoumieu, Catherine Yardin, Valentine Marquet, Marion Barnique, Maryse Fiorenza-Gasq, Isabelle Marey, Danielle Tournadre, Raïa Doumit, Frédérique Nugues, Tahsin Stefan Barakat, Francisco Bustos, Sylvie Jaillard, Erika Launay, Laurent Pasquier, Sylvie Odent","doi":"10.1136/jmg-2024-109854","DOIUrl":"10.1136/jmg-2024-109854","url":null,"abstract":"<p><strong>Introduction: </strong>Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by <i>RLIM</i> variations. Of the 41 patients reported, only 7 antenatal cases were described.</p><p><strong>Method: </strong>After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.</p><p><strong>Results: </strong>We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in <i>RLIM</i>, outside of the two previously known mutational hotspots.</p><p><strong>Conclusion: </strong>Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"824-832"},"PeriodicalIF":3.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large <i>TRAPPC11</i> gene deletions as a cause of muscular dystrophy and their estimated genesis.","authors":"Johana Kopčilová, Hana Ptáčková, Tereza Kramářová, Lenka Fajkusová, Kamila Réblová, Jiří Zeman, Tomáš Honzík, Lucie Zdražilová, Josef Zámečník, Patrícia Balážová, Karin Viestová, Miriam Kolníková, Hana Hansíková, Jana Zídková","doi":"10.1136/jmg-2024-110016","DOIUrl":"10.1136/jmg-2024-110016","url":null,"abstract":"<p><strong>Background: </strong>Transport protein particle (TRAPP) is a multiprotein complex that functions in localising proteins to the Golgi compartment. The TRAPPC11 subunit has been implicated in diseases affecting muscle, brain, eye and to some extent liver. We present three patients who are compound heterozygotes for a missense variant and a structural variant in the <i>TRAPPC11</i> gene. <i>TRAPPC11</i> structural variants have not yet been described in association with a disease. In order to reveal the estimated genesis of identified structural variants, we performed sequencing of individual breakpoint junctions and analysed the extent of homology and the presence of repetitive elements in and around the breakpoints.</p><p><strong>Methods: </strong>Biochemical methods including isoelectric focusing on serum transferrin and apolipoprotein C-III, as well as mitochondrial respiratory chain complex activity measurements, were used. Muscle biopsy samples underwent histochemical analysis. Next-generation sequencing was employed for identifying sequence variants associated with neuromuscular disorders, and Sanger sequencing was used to confirm findings.</p><p><strong>Results: </strong>We suppose that non-homologous end joining is a possible mechanism of deletion origin in two patients and non-allelic homologous recombination in one patient. Analyses of mitochondrial function performed in patients' skeletal muscles revealed an imbalance of mitochondrial metabolism, which worsens with age and disease progression.</p><p><strong>Conclusion: </strong>Our results contribute to further knowledge in the field of neuromuscular diseases and mutational mechanisms. This knowledge is important for understanding the molecular nature of human diseases and allows us to improve strategies for identifying disease-causing mutations.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"908-913"},"PeriodicalIF":3.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>NF2</i>-related schwannomatosis and other schwannomatosis: an updated genetic and epidemiological study.","authors":"Claire Forde, Miriam J Smith, George J Burghel, Naomi Bowers, Nicola Roberts, Tim Lavin, Jane Halliday, Andrew Thomas King, Scott Rutherford, Omar N Pathmanaban, Simon Lloyd, Simon Freeman, Dorothy Halliday, Allyson Parry, Patrick Axon, Juliette Buttimore, Shazia Afridi, Rupert Obholzer, Roger Laitt, Owen Thomas, Stavros Michael Stivaros, Grace Vassallo, D Gareth Evans","doi":"10.1136/jmg-2024-110065","DOIUrl":"10.1136/jmg-2024-110065","url":null,"abstract":"<p><strong>Objectives: </strong>New diagnostic criteria for NF2-related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated in accordance with these, with an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted in genetic counselling). The distribution of variant types among de novo and familial NF2 cases was also assessed.</p><p><strong>Methods: </strong>The UK National NF2 database identifies patients meeting updated NF2 criteria from a highly ascertained population cared for by England's specialised service. Diagnostic prevalence was assessed on 1 February 2023. Molecular analysis of blood and, where possible, tumour specimens for <i>NF2, LZTR1</i> and <i>SMARCB1</i> was performed.</p><p><strong>Results: </strong>1084 living NF2 patients were identified on prevalence day (equivalent to 1 in 61 332). The proportion with NF2 inherited from an affected parent was only 23% in England. If people without a confirmed molecular diagnosis or bilateral vestibular schwannoma are excluded, the frequency of de novo NF2 remains high (72%). Of the identified de novo cases, almost half were mosaic. The most common variant type was nonsense variants, accounting for 173/697 (24.8%) of people with an established variant, but only 18/235 (7.7%) with an inherited <i>NF2</i> pathogenic variant (p<0.0001). Missense variants had the highest proportion of familial association (56%). The prevalence of <i>LZTR1</i>-related schwannomatosis and <i>SMARCB1</i>-related schwannomatosis was 1 in 527 000 and 1 in 1.1M, respectively, 8.4-18.4 times lower than NF2.</p><p><strong>Conclusions: </strong>This work confirms a much higher rate of de novo NF2 than previously reported and highlights the benefits of maintaining patient databases for accurate counselling.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"856-860"},"PeriodicalIF":3.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcellular localisation of truncated MAGEL2 proteins: insight into the molecular pathology of Schaaf-Yang syndrome.","authors":"Mónica Centeno-Pla, Estefanía Alcaide-Consuegra, Sophie Gibson, Aina Prat-Planas, Juan Diego Gutiérrez-Ávila, Daniel Grinberg, Roser Urreizti, Raquel Rabionet, Susanna Balcells","doi":"10.1136/jmg-2024-109898","DOIUrl":"10.1136/jmg-2024-109898","url":null,"abstract":"<p><p>Schaaf-Yang syndrome (SYS) is an ultra-rare neurodevelopmental disorder caused by truncating mutations in <i>MAGEL2</i> Heterologous expression of wild-type (WT) or a truncated (p.Gln638*) C-terminal HA-tagged MAGEL2 revealed a shift from a primarily cytoplasmic to a more nuclear localisation for the truncated protein variant. We now extend this analysis to six additional SYS mutations on a N-terminal FLAG-tagged MAGEL2. Our results replicate and extend our previous findings, showing that all the truncated MAGEL2 proteins consistently display a predominant nuclear localisation, irrespective of the C-terminal or N-terminal position and the chemistry of the tag. The variants associated with arthrogryposis multiplex congenita display a more pronounced nuclear retention phenotype, suggesting a correlation between clinical severity and the degree of nuclear mislocalisation. These results point to a neomorphic effect of truncated MAGEL2, which might contribute to the pathogenesis of SYS.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"780-782"},"PeriodicalIF":3.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carrier testing for partners of <i>MUTYH</i> variant carriers: UK Cancer Genetics Group recommendations.","authors":"Terri Patricia McVeigh, Fiona Lalloo, Kevin J Monahan, Andrew Latchford, Miranda Durkie, Rachael Mein, Emma L Baple, Helen Hanson","doi":"10.1136/jmg-2024-109910","DOIUrl":"10.1136/jmg-2024-109910","url":null,"abstract":"","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"813-816"},"PeriodicalIF":3.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}