Clinical Genetics最新文献

{"title":"Exome Sequencing of Consanguineous Pashtun Families With Familial Epilepsy Reveals Causative and Candidate Variants in TSEN54, MOCS2, and OPHN1","authors":"Afrasiab Khan,&nbsp;Anees Muhammad,&nbsp;Hidayat Ullah,&nbsp;Hina Ambreen,&nbsp;Abeed Ullah,&nbsp;Patrick May,&nbsp;Holger Lerche,&nbsp;Tobias B. Haack,&nbsp;Shoaib ur Rehman,&nbsp;Josua Kegele","doi":"10.1111/cge.14627","DOIUrl":"10.1111/cge.14627","url":null,"abstract":"<p>Next-generation sequencing is advancing in low- and middle-income countries, but accessibility remains limited. In Pakistan, many members of the Pashtun population practice familial marriage and maintain distinct socio-cultural traditions, isolating them from other ethnic groups. As a result, they may harbor genetic variants that could unveil new gene-disease associations. To investigate the genetic basis of epilepsy in the Pashtun community we recently established a collaboration between Bannu University and the University of Tuebingen. Here we report our first results of exome sequencing of four families with presumed monogenetic epilepsy and Mendelian inheritance pattern. In Family #201, we identified distinct disease-causing variants. One had a homozygous pathogenic missense variant in <i>TSEN54</i> (c.919G &gt; T, p.(Ala307Ser)), linked to Pontocerebellar Hypoplasia Type 2A. The second individual had a homozygous class IV missense variant in <i>MOCS2</i> (c.226G &gt; A, p.(Gly76Arg)) which is associated with Molybdenum cofactor deficiency. In family EP02, one affected individual carried a heterozygous class III variant in <i>OPHN1</i> (c.1490G &gt; A, p.(Arg497Gln)), related to syndromic X-linked intellectual disability with epilepsy. Our small study demonstrates the promise of next-generation sequencing in genetic epilepsies among the Pashtun population. Diagnostic next-generation sequencing should be established in Pakistan as soon as possible, and if not feasible, genetic research projects may pioneer this path.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"107 1","pages":"98-103"},"PeriodicalIF":2.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14627","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The p. S178L mutation in Tbc1d24 disrupts endosome-mediated synaptic vesicle trafficking of cochlear hair cells and leads to hearing impairment in mice","authors":"Penghui Chen,&nbsp;Shule Hou,&nbsp;Gen Li,&nbsp;Yuzhe Lin,&nbsp;Jiawen Lu,&nbsp;Lei Song,&nbsp;Geng-Lin Li,&nbsp;Xiuhong Pang,&nbsp;Hao Wu,&nbsp;Tao Yang","doi":"10.1111/cge.14620","DOIUrl":"10.1111/cge.14620","url":null,"abstract":"<p>The ribbon synapses of cochlear inner hair cells (IHCs) employ efficient vesicle resupply to enable fast and sustained release rates. However, the molecular mechanisms of these physiological activities remain unelucidated. Previous studies showed that the RAB-specific GTPase-activating protein <i>TBC1D24</i> controls the endosomal trafficking of the synaptic vesicles (SVs) in <i>Drosophila</i> and mammalian neurons, and mutations in <i>TBC1D24</i> may lead to non-syndromic hearing loss or hearing loss associated with the DOORS syndrome in humans. In this study, we generated a knock-in mouse model for the p. S178L mutation in <i>TBC1D24</i>, which leads to autosomal dominant non-syndromic hearing loss (DFNA65). The p.S178L mutant mice show mild hearing loss and progressively declined wave I amplitude of the auditory brainstem responses. Despite the normal gross and cellular morphology of the cochlea, transmission electron microscopy reveals accumulation of endosome-like vacuoles and a lower-than-normal number of SVs directly associated with the ribbons in the IHCs. Consistently, patch clamp of the IHCs shows reduced exocytosis under prolonged stimulus. ARF6, a <i>TBC1D24</i>-interacting protein also involved in endosomal membrane trafficking, was underexpressed in the cochleae of the mutant mouse and has weakened in vitro interaction with the p.S178L mutant <i>TBC1D24</i>. Our results suggest an important role of <i>TBC1D24</i> in maintaining endosomal-mediated vesicle recycling and sustained exocytosis of hair cell ribbon synapses.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"107 1","pages":"67-77"},"PeriodicalIF":2.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidden Aberrant Transcripts in TTC37 Cause Trichohepatoenteric Syndrome","authors":"José Francisco da Silva Franco,&nbsp;Raquel Leão Neves,&nbsp;Alef Nascimento Menezes,&nbsp;Beatriz Ribeiro Nogueira,&nbsp;Caio Perez Gomes,&nbsp;João Bosco Pesquero","doi":"10.1111/cge.14630","DOIUrl":"10.1111/cge.14630","url":null,"abstract":"<p>The patient had clinical suspicion of THES. Complex genetic analyzes using WES, WGS were performed without success in the diagnosis. Further molecular analyzes using RNA and protein was necessary to reach the final correct THES diagnosis.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"107 1","pages":"113-114"},"PeriodicalIF":2.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consolidating the Role of Mutated ATP2B2 in Neurodevelopmental and Cerebellar Pathologies","authors":"Antonia M. Stehr,&nbsp;Jerica Lenberg,&nbsp;Jennifer Friedman,&nbsp;Dries Dobbelaere,&nbsp;Apolline Imbard,&nbsp;Jonathan Levy,&nbsp;Sarah Donoghue,&nbsp;Nicolas Derive,&nbsp;Radka Stoeva,&nbsp;Paul Gueguen,&nbsp;Michael Zech","doi":"10.1111/cge.14622","DOIUrl":"10.1111/cge.14622","url":null,"abstract":"<p>Plasma membrane calcium ATPases (PMCAs) encoded by <i>ATP2B</i> genes have been implicated in Mendelian diseases with ataxia, dystonia, and intellectual disability. Work to date has shown that <i>ATP2B2</i> (encoding PMCA2) is required for synaptic function and Purkinje-cell integrity in the cerebellum. A recent case series has linked <i>ATP2B2</i> to a novel entity, characterized by neurodevelopmental and movement phenotypes, in only seven individuals. We called for collaboration to collect five unpublished families affected by the new rare <i>ATP2B2</i>-related condition. Exome-/genome sequencing-identified genotypes included four likely pathogenic/pathogenic heterozygous de novo missense variants and one dominantly inherited end-truncating frameshift allele. The six affected individuals shared features with the described patients including developmental delay, cognitive disturbances, epilepsy, autistic traits, and motor disorders. Striking cerebellar atrophy was observed in one affected individual. In association with hearing loss and movement abnormalities, we report a recurrent p.(Glu457Lys) substitution, previously documented in a neurologically impaired <i>ATP2B2</i> mouse mutant. Our study further delineates the mutational spectrum and presentation of a human syndrome caused by <i>ATP2B2</i> variants, confirming the importance of PMCA2 in neurotypical and cerebellar development.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"107 1","pages":"91-97"},"PeriodicalIF":2.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14622","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second Case of Gonadal Mosaicism and a Novel Nonsense NR2F1 Gene Variant as the Cause of Bosch–Boonstra–Schaaf Optic Atrophy Syndrome","authors":"Nenad Hrvatin,&nbsp;Nina Pereza,&nbsp;Tea Čaljkušić-Mance,&nbsp;Tamara Mišljenović Vučerić,&nbsp;Saša Ostojić,&nbsp;Alenka Hodžić,&nbsp;Aleš Maver,&nbsp;Borut Peterlin","doi":"10.1111/cge.14623","DOIUrl":"10.1111/cge.14623","url":null,"abstract":"<div>\u0000 \u0000 <p>Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is an autosomal dominant disease characterized by developmental delay, intellectual disability, and optic atrophy with a variable expression of other clinical features (dysmorphic features, autistic behaviour, corpus callosum hypoplasia and seizures). To date, approximately a hundred cases of the syndrome have been described, with an estimated prevalence of 1 in 100 000–250 000. BBSOAS is caused by the loss of function of the NR2F1 gene (nuclear receptor subfamily 2 group F member 1), which encodes the COUP-TFI (Chicken ovalbumin upstream promotor-transcription factor 1). COUP-TFI functions as a homodimer and is one of the major transcriptional regulators directing cortical arealization, cell differentiation and maturation. Most cases of BBSOAS occur de novo, and one case was previously described in which the disease resulted from gonadal mosaicism. In the present case, we report two sisters with BBSOAS, a novel nonsense mutation in the NR2F1 gene and potential gonadal mosaicism as the cause of this rare disease, making it the second such case described in the literature.</p>\u0000 </div>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 6","pages":"786-787"},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of susceptibility genes in developmental dysplasia of the hip: A comprehensive examination of candidate genes and pathways","authors":"Wenla Wang,&nbsp;Wei Zhuang,&nbsp;Wenxiang Zeng,&nbsp;Yuqi Feng,&nbsp;Zhaowei Zhang","doi":"10.1111/cge.14618","DOIUrl":"10.1111/cge.14618","url":null,"abstract":"<p>Developmental dysplasia of the hip (DDH) is one of the most prevalent skeletal deformities, primarily due to the incompatibility between the acetabulum and femoral head. It includes complete dislocation, partial dislocation, instability with femoral head subluxation, and a range of imaging abnormalities that reflect inadequate acetabular formation. Known risk factors for DDH include positive family history, sex, premature birth, non-cephalic delivery, oligohydramnios, gestational diabetes mellitus, maternal hypertension, associated anomalies, swaddling clothes, intrauterine space restriction, and post-term pregnancy. Various research designs have been employed in DDH studies to identify relevant genes, including candidate gene association studies (CGAS), genome-wide association studies (GWAS), restriction fragment length polymorphism (RFLP), and whole exome sequencing (WES). To date, multiple DDH-associated genes have been identified in various populations. Despite extensive research into the epidemiology, risk factors, and genes associated with DDH, its pathogenesis remains unclear. This study provides a comprehensive summary of DDH research designs and evidence for relevant gene mutations through a PubMed search.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"107 1","pages":"3-12"},"PeriodicalIF":2.9,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel KIF26A variants associated with pediatric intestinal pseudo-obstruction (PIPO) and brain developmental defects","authors":"Mohammad Sadegh Shams Nosrati,&nbsp;Alireza Doustmohammadi,&nbsp;Mariasavina Severino,&nbsp;Ferruccio Romano,&nbsp;Mahdi Zafari,&nbsp;Amir Hesam Nemati,&nbsp;Clara Velmans,&nbsp;Christian Netzer,&nbsp;Jonas Breuer,&nbsp;Ilse Julia Broekaert,&nbsp;Alexander Joachim,&nbsp;Nihad Almasri,&nbsp;Michael C. Kruer,&nbsp;Peter Skidmore,&nbsp;Pritha Bisarad,&nbsp;Jumana Hoque,&nbsp;Somayeh Bakhtiari,&nbsp;Annalaura Torella,&nbsp;Vincenzo Nigro,&nbsp;Francesca Buffelli,&nbsp;Ezio Fulcheri,&nbsp;Annette Müller,&nbsp;Federico Zara,&nbsp;Valeria Capra,&nbsp;Marcello Scala","doi":"10.1111/cge.14621","DOIUrl":"10.1111/cge.14621","url":null,"abstract":"<p>Pediatric intestinal pseudo-obstruction (PIPO) is a rare congenital disorder of the enteric nervous system with distal colon aganglionosis potentially leading to intestinal obstruction. Recently, biallelic variants in <i>KIF26A</i>, encoding a crucial motor protein for the migration and differentiation of enteric neural crest cells, have been associated with a neurodevelopmental condition featuring cortical defects and PIPO-like features, though in absence of aganglionosis. So far, only 10 patients have been reported. In this study, we investigated three subjects with congenital hydrocephalus, neurodevelopmental impairment, and intestinal obstruction megacolon syndrome. Brain MRI revealed malformations within cortical dysplasia spectrum, including polymicrogyria and heterotopia. Pathology study of the intestine revealed aganglionosis and elevated acetylcholinesterase activity in parasympathetic nerve fibers. Through trio-exome sequencing (ES), we detected four novel biallelic <i>KIF26A</i> variants, including two missense changes (#1) and two distinct homozygous truncating variants in (#2 and #3). All variants are rare and predicted to be deleterious according to in silico tools. To characterize the impact of the missense variants, we performed 3D protein modeling using Alphafold3 and YASARA. Mutants exhibited increased energy scores compared to wild-type protein, supporting a significant structural destabilization of the protein. Our study expands the genotype and phenotype spectrum of the emerging <i>KIF26A</i>-related disorder.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"107 1","pages":"83-90"},"PeriodicalIF":2.9,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of the relationship between phosphoprotein phosphatases (PPPs) and neurodevelopmental disorders","authors":"Wenya Ji,&nbsp;Bixia Zheng,&nbsp;Aihua Zhang","doi":"10.1111/cge.14617","DOIUrl":"10.1111/cge.14617","url":null,"abstract":"<p>Reversible protein phosphorylation is a ubiquitous phenomenon essential for eukaryotic cellular processes. Recent advancements in research about neurodevelopmental disorders have prompted investigations into the intricate relationship between protein phosphatases, particularly phosphoprotein phosphatases (PPPs), and neurodevelopment. Notably, variants in 10 coding genes spanning four PPP family members have been implicated in neurodevelopmental disorders. Here, we provide a comprehensive overview of the clinical phenotypes, genotypes, and pathogenic mechanisms observed in affected patients. Our analysis reveals challenges in subsequent statistical analyses due to inconsistent clinical phenotypic descriptions and a lack of large multicenter studies, hampering analysis about genotype–phenotype correlations. The scarcity of follow-up data poses a significant obstacle to prognostic counseling for nearly all rare diseases. Presently, symptomatic treatment strategies are employed for patients with variants, as definitive cures remain elusive. Future research may explore protein phosphatase regulators as potential therapeutic targets. Furthermore, it is imperative not to overlook other members of the protein phosphatase family or coding genes with undiscovered variants. Insights gleaned from the temporal and spatial distribution of proteins, along with observations from animal model phenotypes, may provide valuable directions for uncovering novel pathogenic genes.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 6","pages":"679-692"},"PeriodicalIF":2.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge and perceptions about fragile X syndrome and fragile X-premutation-associated conditions among medical doctors in Nigeria","authors":"Chioma N. P. Mbachu,&nbsp;Randi Hagerman,&nbsp;Edwin Eseigbe,&nbsp;Amalachukwu Odita,&nbsp;Ikechukwu Mbachu,&nbsp;Samuel Ilikanu,&nbsp;Kasarachi Akowundu,&nbsp;Chizalu Ndukwu,&nbsp;Malachy Echezona,&nbsp;Onyedikachi Okereke,&nbsp;Sylvia Echendu,&nbsp;Ifeoma Udigwe","doi":"10.1111/cge.14619","DOIUrl":"10.1111/cge.14619","url":null,"abstract":"<p>Fragile X syndrome (FXS) is a significant cause of intellectual disability and autism, while Fragile X Premutation -Associated Conditions (FXPAC) are a significant cause of morbidity and mortality globally. This study assessed the level of knowledge and perceptions about FXS and FXPAC among doctors in Nigeria. It was a web-based, cross-sectional study conducted among a cohort of doctors in Nigeria. Socio-demographic profile, knowledge of FXS, perceptions about FXS, knowledge of FXPAC, experience of doctors, and suggested ways of improving knowledge and management of FXS were obtained. Data were analyzed using STATA 16.0. Chi-square and Fisher's exact tests of association were used to determine the association between variables, with the significance level set at <i>p</i> &lt; 0.05. A total of 274 doctors participated in the study. A significant proportion of respondents had limited knowledge about the clinical features of FXS. Nine of ten (90.0%) participants with good knowledge of FXS had good perceptions of FXS management. This was statistically significant (<i>p</i> &lt; 0.001). There was a high nonresponse rate to what FXPAC is (164/274, 59.9%) among the respondents because of insufficient knowledge. Suboptimal knowledge of FXS which influenced perception was noted among doctors. More strategies should be considered to improve doctors' knowledge and management of FXS and FXPAC in Nigeria.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"107 1","pages":"56-66"},"PeriodicalIF":2.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14619","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of anomalies of the kidney and urinary tract with congenital heart disease: A review","authors":"Amin J. Barakat,&nbsp;Merlin G. Butler","doi":"10.1111/cge.14615","DOIUrl":"10.1111/cge.14615","url":null,"abstract":"<p>Congenital anomalies of the kidney and urinary tract (CAKUT) and congenital heart disease (CHD) are the most common congenital defects and constitute a major cause of morbidity in children. Anomalies of both systems may be isolated or associated with congenital anomalies of other organ systems. Various reports support the co-occurrence of CAKUT and CHD, although the prevalence can vary. Cardiovascular anomalies occur in 11.2% to 34% of patients with CAKUT, and CAKUT occur in 5.3% to 35.8% of those with CHD. The co-occurrence of genetic factors in both CAKUT and CHD would raise common etiologies including genetics, genetic-environmental interactions, or shared molecular mechanisms and pathways such as NODAL, NOTCH, BMP, WNT, and VEGF. Studies in animal models and humans have indicated a genetic etiology for CHD and CAKUT with hundreds of genes recognized and thousands of entries, found in a catalog of human genetic disorders. There are over 80 CAKUT genes and over 100 CHD genes available for clinical testing. For example, the <i>HNFIB</i> gene accounts for 5% to 31% of reported cases of CAKUT. In view of the association between CAKUT and CHD, a thorough cardiac examination should be performed in patients with CAKUT, and a similar evaluation for CAKUT in the presence of CHD. This will allow early diagnosis and therapeutic intervention to improve the long- term outcome of patients affected, and test for at-risk family members. We present here evidence for an association of anomalies involving the two organ systems, and discuss possible etiologies of targeted genes, their functions, biological processes and interactions on embryogenesis.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 6","pages":"667-678"},"PeriodicalIF":2.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14615","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}