Journal of Medical Genetics最新文献

{"title":"<i>KIF21A</i>-associated peripheral neuropathy defined by impaired binding with TUBB3.","authors":"Nicholas A Borja, Mohammad Faraz Zafeer, Stephanie Bivona, LéShon Peart, Sakir Humayun Gultekin, Guney Bademci, Mustafa Tekin","doi":"10.1136/jmg-2024-109908","DOIUrl":"10.1136/jmg-2024-109908","url":null,"abstract":"<p><p><i>KIF21A</i> encodes a kinesin motor protein associated with isolated congenital fibrosis of the extraocular muscles (CFEOM), which occurs when the autoinhibitory interaction between its motor and third coiled-coil domains is disrupted. In this study, we describe a female child who is heterozygous for a novel de novo missense variant in <i>KIF21A</i> p.Leu664Pro, located in the second coiled-coil domain that was absent in her unaffected parents and in healthy population cohorts. She presented with progressive peripheral neuropathy, hypoplasia of the corpus callosum and strabismus in the absence of CFEOM. Protein modelling predicts that the KIF21A variant leads to significant alterations in its structure as well as binding with TUBB3. Co-immunoprecipitation data was consistent with decreased binding of KIF21A p.Leu664Pro to TUBB3 in vitro compared with reference. Taken together, we delineate a <i>KIF21A</i>-related phenotype defined by progressive peripheral neuropathy, brain anomalies, developmental delay and comitant strabismus potentially stemming from the disruption of the interaction between KIF21A and TUBB3.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"117-122"},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791592","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":"Predicting the likelihood of <i>BRCA1/2</i> germline pathogenic variants in unselected patients with breast cancer: analysis of more than 10,000 individuals.","authors":"Jie Sun, Lu Yao, Jiuan Chen, Li Hu, Juan Zhang, Ye Xu, Yuntao Xie","doi":"10.1136/jmg-2024-110332","DOIUrl":"10.1136/jmg-2024-110332","url":null,"abstract":"<p><strong>Background: </strong>Models for accurately predicting the likelihood of <i>BRCA1/2</i> germline pathogenic variants (PVs) based on a large cohort of unselected patients with breast cancer are limited.</p><p><strong>Methods: </strong>A logistic regression model to predict the <i>BRCA1/2</i> carrier probability, named PKCBRCA, was established and validated based on 10 167 unselected Chinese patients with breast cancer treated in Peking University Cancer Hospital between October 2003 and August 2020. All patients were tested for <i>BRCA1/2</i> germline variants. The discrimination and calibration of the model were assessed.</p><p><strong>Results: </strong>A total of 601 (5.9%) patients carried <i>BRCA1/2</i> germline PVs in the entire cohort of 10 167 unselected patients with breast cancer. The cohort was separated into a training set (n=6331; 387 (6.1%) <i>BRCA1/2</i> carriers) and a validation set (n=3836; 214 (5.6%) <i>BRCA1/2</i> carriers). Five variables strongly associated with <i>BRCA1/2</i> carrier probability were incorporated in the establishment of PKCBRCA including age of diagnosis, bilateral breast cancer, family history of breast or ovarian cancer, hormone receptor and ERBB2. PKCBRCA showed a good ability to discriminate both in the training set (area under the receiver operating characteristic curve (AUC)=0.77) and in the validation set (AUC=0.77).</p><p><strong>Conclusion: </strong>Our model provides a useful tool for accurately assessing the <i>BRCA1/2</i> carrier probability for unselected patients with breast cancer.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"62-68"},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812984","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":"Hiding in plain sight: a partial deletion of <i>BRCA1</i> exon 7 undetectable by MLPA is a Nepali founder variant.","authors":"Virginia Clowes, Jenny C Taylor, Alistair T Pagnamenta","doi":"10.1136/jmg-2024-110422","DOIUrl":"10.1136/jmg-2024-110422","url":null,"abstract":"","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"54-56"},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812590","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":"Retrospective study on the utility of optical genome mapping as a follow-up method in genetic diagnostics.","authors":"Paul Dremsek, Anna Schachner, Theresa Reischer, Elisabeth Krampl-Bettelheim, Dieter Bettelheim, Sybille Vrabel, Zoja Delissen, Mateja Pfeifer, Beatrix Weil, Robert Bajtela, Markus Hengstschläger, Franco Laccone, Jürgen Neesen","doi":"10.1136/jmg-2024-110265","DOIUrl":"10.1136/jmg-2024-110265","url":null,"abstract":"<p><strong>Background: </strong>Current standard-of-care (SOC) methods for genetic testing are capable of resolving deletions and sequence variants, but they mostly fail to provide information on the breakpoints of duplications and balanced structural variants (SV). However, this information may be necessary for their clinical assessment, especially if the carrier's phenotype is difficult to assess and/or carrier analysis of relatives is not viable. A promising approach to solving such challenging cases arises with access to optical genome mapping (OGM) but has not been systematically explored as of yet.</p><p><strong>Methods: </strong>In this retrospective study, we evaluated diagnostic cases from a 1-year period (2023) in which an SV discovery by SOC methods (microarray, karyotyping and whole-exome sequencing) was followed up by OGM, with the objective to unlock clinically relevant information about the SV.</p><p><strong>Results: </strong>Seven cases were shown by SOC methods to bear potential pathogenic SVs and were consequently followed up by OGM. Of these, six were solved by the additional use of OGM alone. One case required sequencing after OGM analysis to further specify the SV's breakpoints. In all seven cases, OGM was crucial for determining the clinical relevance of the detected SV.</p><p><strong>Conclusion: </strong>This study describes the use of OGM as a valuable method for characterising duplications and balanced SVs. Often, this additional information does not add to the quality of a clinical report. However, for a subset of patients, these data are critical, especially in the prenatal setting or when no familial analyses are possible.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"89-96"},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801133","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":"Aortic and arterial manifestations and clinical features in <i>TGFB3</i>-related heritable thoracic aortic disease: results from the Montalcino Aortic Consortium.","authors":"Michelle Su-Anne Lim, Dong-Chuan Guo, Walter Velasco Torrez, Andrew Lai, Jonathan Schweber, Nikita Garg, Julie Fleischer, Catherine Boileau, Julie De Backer, Artur Evangelista, Guillaume Jondeau, Carine Le Goff, Olivier Milleron, Laura Muiño-Mosquera, Shaine Morris, Maral Ouzounian, Elena Cervi, Julien Marcadier, Anthony Caffarelli, Sherene Shalhub, Reed Pyeritz, Angela Yetman, Dianna Milewicz, Alan C Braverman","doi":"10.1136/jmg-2024-110251","DOIUrl":"10.1136/jmg-2024-110251","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic variants in <i>TGFB3</i> may lead to a syndromic genetic aortopathy. Heritable thoracic aortic disease (HTAD) and arterial events may occur in <i>TGFB3</i>-related disease but there are limited outcomes data on vascular events in this condition.</p><p><strong>Methods: </strong>Clinical data, phenotypical features and aortic outcomes in individuals with pathogenic/likely pathogenic (P/LP) <i>TGFB3</i> variants enrolled in the Montalcino Aortic Consortium registry were reviewed.</p><p><strong>Results: </strong>34 individuals (56% male, median age 42 years, IQR 17-49, range 3-74 years) with P/LP <i>TGFB3</i> variants were studied. Craniofacial, cutaneous and musculoskeletal features seen in Loeys-Dietz syndrome were variably present. Extra-aortic cardiovascular features included arterial tortuosity (25%), extra-aortic arterial aneurysms (6%) and mitral valve prolapse (21%).Aortic dilation (Z-Score>2) was present in 10 individuals (29%) and aortic dissection occurred in 2 (6%). Type A aortic dissection occurred in two patients (aged between 55 years and 60 years), and one of these patients experienced a type B aortic dissection 6 years later. Seven adults (median age 62 years, range 32-69 years) with aortic root dilation (41-49 mm) are being followed. No patients have undergone prophylactic aortic surgery. Twenty-five per cent of children have aortic dilation. Sixty-eight per cent of the entire cohort remains free of aortic disease. No deaths have occurred.</p><p><strong>Conclusions: </strong><i>TGFB3</i>-related HTAD is characterised by late-onset and less penetrant thoracic aortic and arterial disease compared with other transforming growth factor β HTAD. Based on our data, a larger aortic size threshold for prophylactic aortic surgery is appropriate in patients with <i>TGFB3</i>-related HTAD compared with HTAD due to <i>TGFBR1</i> or <i>TGFBR2</i> variants.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"82-88"},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801128","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>TFAP2E</i> is implicated in central nervous system, orofacial and maxillofacial anomalies.","authors":"Jeshurun C Kalanithy, Enrico Mingardo, Jil D Stegmann, Ramgopal Dhakar, Tikam Chand Dakal, Jill A Rosenfeld, Wen-Hann Tan, Stephanie A Coury, Audrey C Woerner, Jessica Sebastian, Paul A Levy, Leah R Fleming, Lea Waffenschmidt, Tobias T Lindenberg, Öznur Yilmaz, Khadija Channab, Bimaljeet K Babra, Andrea Christ, Britta Eiberger, Selina Hölzel, Clara Vidic, Felix Häberlein, Nina Ishorst, Juan E Rodriguez-Gatica, Behnaz Pezeshkpoor, Patrick A Kupczyk, Olivier M Vanakker, Sara Loddo, Antonio Novelli, Maria L Dentici, Albert Becker, Holger Thiele, Jennifer E Posey, James R Lupski, Alina C Hilger, Heiko M Reutter, Waltraut M Merz, Gabriel C Dworschak, Benjamin Odermatt","doi":"10.1136/jmg-2023-109799","DOIUrl":"10.1136/jmg-2023-109799","url":null,"abstract":"<p><strong>Background: </strong>Previous studies in mouse, <i>Xenopus</i> and zebrafish embryos show strong <i>tfap2e</i> expression in progenitor cells of neuronal and neural crest tissues suggesting its involvement in neural crest specification. However, the role of human transcription factor activator protein 2 (<i>TFAP2E)</i> in human embryonic central nervous system (CNS), orofacial and maxillofacial development is unknown.</p><p><strong>Methods: </strong>Through a collaborative work, exome survey was performed in families with congenital CNS, orofacial and maxillofacial anomalies. Exome variant prioritisation prompted <i>TFAP2E</i> gene for functional analysis in zebrafish embryos. Embryonic morphology and development were assessed after antisense morpholino (MO) knockdown (KD), CRISPR/Cas9 knockout and overexpression of <i>tfap2e</i> in fluorescent zebrafish reporter lines using in vivo microscopy. Computational structural protein modelling of the identified human variants was performed.</p><p><strong>Results: </strong>In total, exome survey identified novel or ultra-rare heterozygous missense variants in <i>TFAP2E</i> in seven individuals from five independent families with predominantly CNS, orofacial and maxillofacial anomalies. One variant was found de novo and another variant segregated in an affected multiplex family. Protein modelling of the identified variants indicated potential distortion of TFAP2E in the transactivation or dimerisation domain. MO KD and CRISPR/Cas9 knockout of <i>tfap2e</i> in zebrafish revealed hydrocephalus and a significant reduction of brain volume, consistent with a microencephaly phenotype. Furthermore, mRNA overexpression of <i>TFAP2E</i> indicates dosage-sensitive phenotype expression. In addition, zebrafish showed orofacial and maxillofacial anomalies following <i>tfap2e</i> KD, recapitulating the human phenotype.</p><p><strong>Conclusion: </strong>Our human genetic data and analysis of Tfap2e manipulation in zebrafish indicate a potential role of <i>TFAP2E</i> in human CNS, orofacial and maxillofacial anomalies.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"126-137"},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11777392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881570","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":"Validation of the NCCN/Yale criteria for the identification of <i>CDH1</i> pathogenic variant carriers.","authors":"Benjamin A Lerner, Mar Giner-Calabuig, Cassidy Carraway, Marcy Richardson, Karl Krahn, Lisa Susswein, Sarah M Nielsen, Rachid Karam, Rosa M Xicola, Xavier Llor","doi":"10.1136/jmg-2024-110446","DOIUrl":"10.1136/jmg-2024-110446","url":null,"abstract":"<p><strong>Background: </strong>Diffuse gastric and lobular breast cancer (LBC) syndrome is an autosomal-dominant syndrome characterised by early-onset diffuse gastric cancer and LBC most often caused by germline pathogenic variants (PVs) in <i>CDH1</i>. We previously showed the International Gastric Cancer Linkage Consortium (IGCLC) criteria for genetic testing to have poor sensitivity for <i>CDH1</i> PV and proposed our own simpler and more sensitive Yale criteria. The European Reference Network on Genetic Tumour Risk Syndromes subsequently proposed expanding the IGCLC criteria and showed its LBC-expanded criteria to be more sensitive than the IGCLC criteria in a European cohort of <i>CDH1</i> PV carriers.</p><p><strong>Methods: </strong>We aggregated demographic and clinical data of all <i>CDH1</i> PV carriers identified at three US commercial laboratories. These data were used to calculate the sensitivity of the IGCLC, LBC-expanded and National Comprehensive Cancer Network (NCCN)/Yale criteria.</p><p><strong>Results: </strong>Data on 708 probands and their 4318 family members were included in the analysis. In this cohort, the sensitivities for detecting <i>CDH1</i> PVs were 23.6% for IGCLC criteria, 35.7% for LBC-expanded criteria and 82.2% for NCCN/Yale criteria.</p><p><strong>Conclusion: </strong>In a large cohort of <i>CDH1</i> PV carriers to date, the IGCLC and LBC-expanded criteria called for genetic testing in a minority of <i>CDH1</i> PV carriers while the Yale criteria detected the large majority. Along with their superior sensitivity, the NCCN/Yale criteria address critical practical challenges in cancer genetics by not depending heavily on pathology information from family members which is often lacking and by incorporating recommendations from other cancer genetics guidelines.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"57-61"},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824250","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":"A tandem duplication of exon 42 of the <i>DMD</i> gene is a likely benign variant.","authors":"Jesse B G Hayesmoore, Ruth Newbury-Ecob, Sarah Durell, Amy Dillon, Farah Kanani, Fiona Beecroft, Joanna Jarvis, Deirdre Cilliers, Carl Fratter","doi":"10.1136/jmg-2024-110159","DOIUrl":"10.1136/jmg-2024-110159","url":null,"abstract":"","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"123-125"},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881586","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":"Novel <i>HYLS1</i> variants associated with Joubert syndrome suggest potential genotype-phenotype correlates.","authors":"Simone Gana, Fulvio D'Abrusco, Roberta Nicotra, Chiara Ghiberti, Guido Catalano, Elisa Rognone, Anna Pichiecchio, Sabrina Signorini, Enza Maria Valente","doi":"10.1136/jmg-2024-110308","DOIUrl":"10.1136/jmg-2024-110308","url":null,"abstract":"<p><p>Joubert syndrome (JS) is an inherited neurodevelopmental ciliopathy with wide clinical and genetic heterogeneity, whose paradigmatic sign is a peculiar cerebellar and brainstem malformation known as the 'molar tooth sign'. Recessive pathogenic variants in the <i>HYLS1</i> gene are associated with hydrolethalus syndrome (HLS), a severe disorder characterised by multiple developmental defects leading to intrauterine or perinatal death. However, <i>HYLS1</i> biallelic variants were also reported in three individuals with JS.Here, we report a fourth patient with a purely neurological JS carrying two compound heterozygous missense variants in the <i>HYLS1</i> gene. Notably, while all patients with lethal HLS had both variants falling within the highly conserved HYLS-1 Box, the four patients with milder JS phenotype featured at least one variant external to this evolutionary conserved domain, suggesting a possible correlation between the mutation site and the severity of the phenotype.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"3-5"},"PeriodicalIF":3.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769786","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":"Enhancing variant of uncertain significance (VUS) interpretation in neurogenetics: collaborative experiences from a tertiary care centre.","authors":"Kayla Horowitz, Nellie H Fotopoulos, Alana J Mistry, Justin Simo, Miranda Medeiros, Isabela D Bucco, Mia Ginsberg, Emily Dwosh, Roberta La Piana, Guy A Rouleau, Allison A Dilliott, Sali M K Farhan","doi":"10.1136/jmg-2024-110122","DOIUrl":"10.1136/jmg-2024-110122","url":null,"abstract":"<p><strong>Background: </strong>The findings of variants of uncertain significance (VUS) on a clinical genetic testing report pose a challenge for attending healthcare professionals (HCPs) in patient care. Here, we describe the outcomes of multidisciplinary VUS Rounds, implemented at a neurological disease tertiary care centre, which aid in interpreting and communicating VUS identified in our neurogenetics patient population.</p><p><strong>Methods: </strong>VUS Rounds brought together genetic counsellors, molecular geneticists and scientists to evaluate VUS against genomic and phenotypic evidence and assign an internal temperature classification of 'VUS Hot', 'True VUS' or 'VUS Cold', corresponding to potential pathogenicity. Biweekly meetings were held among the committee to deliberate variant classifications, determine additional clinical management actions and discuss nuances of VUS result communication.</p><p><strong>Results: </strong>In total, 143 VUS identified in 72 individuals with neurological disease were curated between October 2022 and December 2023. Of these, 12.6% were classified as VUS Hot, carried by 22.2% of the individuals, allowing for prioritisation of additional evaluation to determine potential pathogenicity of the variants, such as clinical follow-up or segregation analysis. In contrast, 45.4% of VUS were Cold and could be eliminated from further consideration in the carrier's care. We thoroughly evaluated the various evidence that contributed to our VUS classifications and resulting clinical actions.</p><p><strong>Conclusions: </strong>The assessment of VUS leveraging multidisciplinary collaboration allowed us to delineate required follow-up analyses for our neurology patient population. Integration of VUS Rounds into healthcare practices ensures equitable knowledge dissemination among HCPs and effective incorporation of uncertain genetic results into patient care.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"37-45"},"PeriodicalIF":3.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639215","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}