Journal of Medical Genetics最新文献

{"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}

{"title":"A comparative medical genomics approach may facilitate the interpretation of rare missense variation.","authors":"Bushra Haque, George Guirguis, Meredith Curtis, Hera Mohsin, Susan Walker, Michelle M Morrow, Gregory Costain","doi":"10.1136/jmg-2023-109760","DOIUrl":"10.1136/jmg-2023-109760","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the degree to which likely causal missense variants of single-locus traits in domesticated species have features suggestive of pathogenicity in a human genomic context.</p><p><strong>Methods: </strong>We extracted missense variants from the Online Mendelian Inheritance in Animals database for nine animals (cat, cattle, chicken, dog, goat, horse, pig, rabbit and sheep), mapped coordinates to the human reference genome and annotated variants using genome analysis tools. We also searched a private commercial laboratory database of genetic testing results from >400 000 individuals with suspected rare disorders.</p><p><strong>Results: </strong>Of 339 variants that were mappable to the same residue and gene in the human genome, 56 had been previously classified with respect to pathogenicity: 31 (55.4%) pathogenic/likely pathogenic, 1 (1.8%) benign/likely benign and 24 (42.9%) uncertain/other. The odds ratio for a pathogenic/likely pathogenic classification in ClinVar was 7.0 (95% CI 4.1 to 12.0, p<0.0001), compared with all other germline missense variants in these same 220 genes. The remaining 283 variants disproportionately had allele frequencies and REVEL scores that supported pathogenicity.</p><p><strong>Conclusion: </strong>Cross-species comparisons could facilitate the interpretation of rare missense variation. These results provide further support for comparative medical genomics approaches that connect big data initiatives in human and veterinary genetics.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"817-821"},"PeriodicalIF":3.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175023","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":"Comprehensive preimplantation genetic testing for balanced insertional translocation carriers.","authors":"Shuo Zhang, Zhenle Pei, Min Xiao, Jing Zhou, Bin Hu, Saijuan Zhu, Xiaoxi Sun, Junping Wu, Caixia Lei, Congjian Xu","doi":"10.1136/jmg-2024-109851","DOIUrl":"10.1136/jmg-2024-109851","url":null,"abstract":"<p><strong>Background: </strong>Balanced insertional translocations (BITs) can increase the risk of infertility, recurrent miscarriages or neonatal birth defects due to chromosomal imbalances in gametes. However, studies on preimplantation genetic testing (PGT) for patients carrying BITs are inadequate.</p><p><strong>Methods: </strong>A preimplantation genetic genotyping and haplotype analysis approach was developed and implemented in this study. Genome-wide SNP genotyping was performed, followed by core family-based haplotype analysis. The balanced insertion segments in euploid embryos were inferred from the haplotypes inherited from the carrier parent.</p><p><strong>Results: </strong>A total of 10 BIT carrier couples were enrolled in our study. 15 in vitro fertilisation cycles were conducted, resulting in 73 blastocysts biopsied and subjected to PGT analysis. Among these, 20 blastocysts displayed rearrangement-related imbalances, 13 exhibited de novo aneuploidies, 15 presented a complex anomaly involving both imbalances and additional aneuploidies, while 25 were euploid. Within the euploid embryos, 12 were balanced carrier embryos and 13 were non-carrier embryos. To date, eight non-carrier and one carrier embryos have been transferred, resulting in seven clinical pregnancies. All pregnancies were recommended to perform prenatal diagnosis, our date revealed complete concordance between fetal genetic testing results and PGT results. Presently, five infants have been born from these pregnancies, and two pregnancies are still ongoing.</p><p><strong>Conclusion: </strong>The proposed method facilitates comprehensive chromosome screening and the concurrent identification of balanced insertions or normal karyotypes in embryos. This study offers an effective and universally applicable strategy for BIT carriers to achieve a healthy pregnancy and prevent the transmission of BITs to their offspring.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"794-802"},"PeriodicalIF":3.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158143","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":"Guidelines for NGS procedures applied to prenatal diagnosis by the Spanish Society of Gynecology and Obstetrics and the Spanish Association of Prenatal Diagnosis.","authors":"Anna Abulí, Eugenia Antolín, Antoni Borrell, Maria Garcia-Hoyos, Fe García Santiago, Irene Gómez Manjón, Nerea Maíz, Cristina González González, Laia Rodríguez-Revenga, Irene Valenzuena Palafoll, Javier Suela","doi":"10.1136/jmg-2024-109878","DOIUrl":"10.1136/jmg-2024-109878","url":null,"abstract":"<p><strong>Objective: </strong>This document addresses the clinical application of next-generation sequencing (NGS) technologies for prenatal genetic diagnosis and aims to establish clinical practice recommendations in Spain to ensure uniformity in implementing these technologies into prenatal care.</p><p><strong>Methods: </strong>A joint committee of expert obstetricians and geneticists was created to review the existing literature on fetal NGS for genetic diagnosis and to make recommendations for Spanish healthcare professionals.</p><p><strong>Results: </strong>This guideline summarises technical aspects of NGS technologies, clinical indications in prenatal setting, considerations regarding findings to be reported, genetic counselling considerations as well as data storage and protection policies.</p><p><strong>Conclusions: </strong>This document provides updated recommendations for the use of NGS diagnostic tests in prenatal diagnosis. These recommendations should be periodically reviewed as our knowledge of the clinical utility of NGS technologies, applied during pregnancy, may advance.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"727-733"},"PeriodicalIF":3.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247235","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":"Heterozygous deletion of <i>HOXC10-HOXC9</i> causes lower limb abnormalities in congenital vertical talus.","authors":"Liheng Chen, Shuoyang Zhao, Wenxia Song, Lihong Wang, Zerong Yao, Jianfei Gao, Xiaoze Li","doi":"10.1136/jmg-2023-109656","DOIUrl":"10.1136/jmg-2023-109656","url":null,"abstract":"","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"777-779"},"PeriodicalIF":3.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650910","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":"Variant classification changes over time in the clinical molecular diagnostic laboratory setting.","authors":"Elan Hahn, Chloe Mighton, Yael Fisher, Andrew Wong, Vanessa Di Gioacchino, Nicholas Watkins, Justin Mayers, Yvonne Bombard, George S Charames, Jordan Lerner-Ellis","doi":"10.1136/jmg-2023-109772","DOIUrl":"10.1136/jmg-2023-109772","url":null,"abstract":"<p><strong>Background: </strong>Variant classification in the setting of germline genetic testing is necessary for patients and their families to receive proper care. Variants are classified as pathogenic (P), likely pathogenic (LP), uncertain significance (VUS), likely benign (LB) and benign (B) using the standards and guidelines recommended by the American College of Medical Genetics and the Association for Molecular Pathology, with modifications for specific genes. As the literature continues to rapidly expand, and evidence continues to accumulate, prior classifications can be updated accordingly. In this study, we aim to characterise variant reclassifications in Ontario.</p><p><strong>Methods: </strong>DNA samples from patients seen at hereditary cancer clinics in Ontario from January 2012 to April 2022 were submitted for testing. Patients met provincial eligibility criteria for testing for hereditary cancer syndromes or polycystic kidney disease. Reclassification events were determined to be within their broader category of significance (B to LB or vice versa, or P to LP or vice versa) or outside of their broader category as significance (ie, significant reclassifications from B/LB or VUS or P/LP, from P/LP to VUS or B/LB, or from VUS to any other category).</p><p><strong>Results: </strong>Of the 8075 unique variants included in this study, 23.7% (1912) of variants were reassessed, and 7.2% (578) of variants were reclassified. Of these, 351 (60.7%) variants were reclassified outside of their broader category of significance. Overall, the final classification was significantly different for 336 (58.1%) variants. Importantly, most reclassified variants were downgraded to a more benign classification (n=245; 72.9%). Of note, most reclassified VUS was downgraded to B/LB (n=233; 84.7%).</p><p><strong>Conclusions: </strong>The likelihood for reclassification of variants on reassessment is high. Most reclassified variants were downgraded to a more benign classification. Our findings highlight the importance of periodic variant reassessment to ensure timely and appropriate care for patients and their families.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"788-793"},"PeriodicalIF":3.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160573","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":"Validation of the BOADICEA model in a prospective cohort of <i>BRCA1/2</i> pathogenic variant carriers.","authors":"Xin Yang, Thea M Mooij, Goska Leslie, Lorenzo Ficorella, Nadine Andrieu, Karin Kast, Christian F Singer, Anna Jakubowska, Carla H van Gils, Yen Y Tan, Christoph Engel, Muriel A Adank, Christi J van Asperen, Margreet G E M Ausems, Pascaline Berthet, Margriet J Collee, Jackie A Cook, Jacqueline Eason, Karin Y van Spaendonck-Zwarts, D Gareth Evans, Encarna B Gómez García, Helen Hanson, Louise Izatt, Zoe Kemp, Fiona Lalloo, Christine Lasset, Fabienne Lesueur, Hannah Musgrave, Sophie Nambot, Catherine Noguès, Jan C Oosterwijk, Dominique Stoppa-Lyonnet, Marc Tischkowitz, Vishakha Tripathi, Marijke R Wevers, Emily Zhao, Flora E van Leeuwen, Marjanka K Schmidt, Douglas F Easton, Matti A Rookus, Antonis C Antoniou","doi":"10.1136/jmg-2024-109943","DOIUrl":"10.1136/jmg-2024-109943","url":null,"abstract":"<p><strong>Background: </strong>No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in <i>BRCA1/2</i> pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort of <i>BRCA1/2</i> PV carriers ascertained through clinical genetic centres.</p><p><strong>Methods: </strong>We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614 <i>BRCA1</i> and 1365 <i>BRCA2</i> PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 SNPs and family history information.</p><p><strong>Results: </strong>The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E/O=1.07, 95% CI: 0.92 to 1.24) and in quintiles of predicted risk. Discrimination was maximised when all risk factors were considered (Harrell's C-index=0.70, 95% CI: 0.67 to 0.74; area under the curve=0.79, 95% CI: 0.76 to 0.82). The model performance was similar when evaluated separately in <i>BRCA1</i> or <i>BRCA2</i> PV carriers. The full model identified 5.8%, 12.9% and 24.0% of <i>BRCA1/2</i> PV carriers with 5-year breast cancer risks of <1.65%, <3% and <5%, respectively, risk thresholds commonly used for different management and risk-reduction options.</p><p><strong>Conclusion: </strong>BOADICEA may be used to aid personalised cancer risk management and decision-making for <i>BRCA1</i> and <i>BRCA2</i> PV carriers. It is implemented in the free-access CanRisk tool (https://www.canrisk.org/).</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"803-809"},"PeriodicalIF":3.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247237","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":"ZFYVE19 deficiency: a ciliopathy involving failure of cell division, with cell death.","authors":"Jing Yang, Ya-Nan Zhang, Ren-Xue Wang, Chen-Zhi Hao, Yiling Qiu, Hao Chi, Wei-Sha Luan, HongYi Tang, Xiu-Juan Zhang, XuXu Sun, Jonathan A Sheps, Victor Ling, Muqing Cao, Jian-She Wang","doi":"10.1136/jmg-2023-109779","DOIUrl":"10.1136/jmg-2023-109779","url":null,"abstract":"<p><strong>Background and aims: </strong>Variants in <i>ZFYVE19</i> underlie a disorder characterised by progressive portal fibrosis, portal hypertension and eventual liver decompensation. We aim to create an animal model to elucidate the pathogenic mechanism.</p><p><strong>Methods: </strong><i>Zfyve19</i> knockout (<i>Zfyve19^-/-</i> ) mice were generated and exposed to different liver toxins. Their livers were characterised at the tissue, cellular and molecular levels. Findings were compared with those in wild-type mice and in ZFYVE19-deficient patients. <i>ZFYVE19</i> knockout and knockdown retinal pigment epithelial-1 cells and mouse embryonic fibroblasts were generated to study cell division and cell death.</p><p><strong>Results: </strong>The <i>Zfyve19^-/-</i> mice were normal overall, particularly with respect to hepatobiliary features. However, when challenged with α-naphthyl isothiocyanate, <i>Zfyve19^-/-</i> mice developed changes resembling those in ZFYVE19-deficient patients, including elevated serum liver injury markers, increased numbers of bile duct profiles with abnormal cholangiocyte polarity and biliary fibrosis. Failure of cell division, centriole and cilia abnormalities, and increased cell death were observed in knockdown/knockout cells. Increased cell death and altered mRNA expression of cell death-related signalling pathways was demonstrated in livers from <i>Zfyve19^-/-</i> mice and patients. Transforming growth factor-β (TGF-β) and Janus kinase-Signal Transducer and Activator of Transcription 3 (JAK-STAT3) signalling pathways were upregulated in vivo, as were chemokines such as C-X-C motif ligands 1, 10 and 12.</p><p><strong>Conclusions: </strong>Our findings demonstrated that ZFYVE19 deficiency is a ciliopathy with novel histological features. Failure of cell division with ciliary abnormalities and cell death activates macrophages and may thus lead to biliary fibrosis via TGF-β pathway in the disease.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"750-758"},"PeriodicalIF":3.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179442","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}