Neurogenetics最新文献

{"title":"Power of NGS-based tests in HSP diagnosis: analysis of massively parallel sequencing in clinical practice.","authors":"Daniele Galatolo,&nbsp;Rosanna Trovato,&nbsp;Arianna Scarlatti,&nbsp;Salvatore Rossi,&nbsp;Gemma Natale,&nbsp;Giovanna De Michele,&nbsp;Melissa Barghigiani,&nbsp;Ettore Cioffi,&nbsp;Alessandro Filla,&nbsp;Giusi Bilancieri,&nbsp;Carlo Casali,&nbsp;Filippo M Santorelli,&nbsp;Gabriella Silvestri,&nbsp;Alessandra Tessa","doi":"10.1007/s10048-023-00717-9","DOIUrl":"10.1007/s10048-023-00717-9","url":null,"abstract":"<p><p>Hereditary spastic paraplegia (HSP) refers to a group of heterogeneous neurological disorders mainly characterized by corticospinal degeneration (pure forms), but sometimes associated with additional neurological and extrapyramidal features (complex HSP). The advent of next-generation sequencing (NGS) has led to huge improvements in knowledge of HSP genetics and made it possible to clarify the genetic etiology of hundreds of \"cold cases,\" accelerating the process of reaching a molecular diagnosis. The different NGS-based strategies currently employed as first-tier approaches most commonly involve the use of targeted resequencing panels and exome sequencing, whereas genome sequencing remains a second-tier approach because of its high costs. The question of which approach is the best is still widely debated, and many factors affect the choice. Here, we aim to analyze the diagnostic power of different NGS techniques applied in HSP, by reviewing 38 selected studies in which different strategies were applied in different-sized cohorts of patients with genetically uncharacterized HSP.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 3","pages":"147-160"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9847833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sub-region analysis of DMD gene in cases with idiopathic generalized epilepsy.","authors":"Zhi-Jian Lin,&nbsp;Bi-Xia Huang,&nbsp;Li-Fang Su,&nbsp;Sheng-Yin Zhu,&nbsp;Jun-Wei He,&nbsp;Guo-Zhang Chen,&nbsp;Peng-Xing Lin","doi":"10.1007/s10048-023-00715-x","DOIUrl":"10.1007/s10048-023-00715-x","url":null,"abstract":"<p><p>Gene sub-region encoded protein domain is the basic unit for protein structure and function. The DMD gene is the largest coding gene in humans, with its phenotype relevant to idiopathic generalized epilepsy. We hypothesized variants clustered in sub-regions of idiopathic generalized epilepsy genes and investigated the relationship between the DMD gene and idiopathic generalized epilepsy. Whole exome sequencing was performed in 106 idiopathic generalized epilepsy individuals. DMD variants were filtered with variant type, allele frequency, in silico prediction, hemizygous or homozygous status in the population, inheritance mode, and domain location. Variants located at the sub-regions were selected by the subRVIS software. The pathogenicity of variants was evaluated by the American College of Medical Genetics and Genomics criteria. Articles on functional studies related to epilepsy for variants clustered protein domains were reviewed. In sub-regions of the DMD gene, two variants were identified in two unrelated cases with juvenile absence epilepsy or juvenile myoclonic epilepsy. The pathogenicity of both variants was uncertain significance. Allele frequency of both variants in probands with idiopathic generalized epilepsy reached statistical significance compared with the population (Fisher's test, p = 2.02 × 10^-6, adjusted α = 4.52 × 10^-6). The variants clustered in the spectrin domain of dystrophin, which binds to glycoprotein complexes and indirectly affects ion channels contributing to epileptogenesis. Gene sub-region analysis suggests a weak association between the DMD gene and idiopathic generalized epilepsy. Functional analysis of gene sub-region helps infer the pathogenesis of idiopathic generalized epilepsy.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 3","pages":"161-169"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10148559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSEN1/SLC20A2 double mutation causes early-onset Alzheimer's disease and primary familial brain calcification co-morbidity.","authors":"Sophie Hebestreit,&nbsp;Janine Schwahn,&nbsp;Vesile Sandikci,&nbsp;Mate E Maros,&nbsp;Ivan Valkadinov,&nbsp;Rüstem Yilmaz,&nbsp;Lukas Eckrich,&nbsp;Seyed Babak Loghmani,&nbsp;Hendrik Lesch,&nbsp;Julian Conrad,&nbsp;Holger Wenz,&nbsp;Anne Ebert,&nbsp;David Brenner,&nbsp;Jochen H Weishaupt","doi":"10.1007/s10048-023-00723-x","DOIUrl":"10.1007/s10048-023-00723-x","url":null,"abstract":"<p><p>Primary familial brain calcification (PFBC; formerly Fahr's disease) and early-onset Alzheimer's disease (EOAD) may share partially overlapping pathogenic principles. Although the heterozygous loss-of-function mutation c.1523 + 1G > T in the PFBC-linked gene SLC20A2 was detected in a patient with asymmetric tremor, early-onset dementia, and brain calcifications, CSF β-amyloid parameters and FBB-PET suggested cortical β-amyloid pathology. Genetic re-analysis of exome sequences revealed the probably pathogenic missense mutation c.235G > A/p.A79T in PSEN1. The SLC20A2 mutation segregated with mild calcifications in two children younger than 30 years. We thus describe the stochastically extremely unlikely co-morbidity of genetic PFBC and genetic EOAD. The clinical syndromes pointed to additive rather than synergistic effects of the two mutations. MRI data revealed the formation of PFBC calcifications decades before the probable onset of the disease. Our report furthermore exemplifies the value of neuropsychology and amyloid PET for differential diagnosis.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 3","pages":"209-213"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10319679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characterization of familial 1p36.3 microduplication.","authors":"Junping Jiao,&nbsp;Yuping Wang,&nbsp;Yue Hou,&nbsp;Chao Gao,&nbsp;Huimin Shi,&nbsp;Shujuan Tian","doi":"10.1007/s10048-023-00722-y","DOIUrl":"10.1007/s10048-023-00722-y","url":null,"abstract":"<p><p>Unlike the 1p36 microdeletion syndrome, which has been extensively described, 1p36.3 microduplications have rarely been reported. We report the two siblings of familial 1p36.3 microduplication, presenting with a severe global developmental delay, epilepsy, and a few dysmorphic features. They were referred to moderate-to-severe developmental delay (DD) and intellectual disability (ID). Both were considered eyelid myoclonus with absence of epilepsy (Jeavons syndrome). The EEG is characterized by widespread 2.5-3.5 Hz spikes and spike slow complex wave, eye closure sensitivity, and photosensitivity. The children has same dysmorphic features, including mild bitemporal narrowing and sloping forehead, sparse eyebrows, hypertelorism, ptosis, strabismus, infraorbital creases, wide nasal bridge with bulbous nasal tip, dystaxia, hallux valgus, and flat feet. Family exome sequencing revealed a maternally inherited 3.2-Mb microduplication of chromosomal band 1p36.3p36.2. However, DNA purified from blood samples of either parent did not find evidence for a microduplication of 1p36 in somatic tissue, indicating that such a mutation might be carried in the germline of the parents as gonadal mosaicism. No other family members of the affected siblings' parents were reported to be affected by the symptoms found.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 3","pages":"201-208"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10319691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A deep intronic variant in DNM1 in a patient with developmental and epileptic encephalopathy creates a splice acceptor site and affects only transcript variants including exon 10a.","authors":"Frederike L Harms,&nbsp;Deike Weiss,&nbsp;Jasmin Lisfeld,&nbsp;Malik Alawi,&nbsp;Kerstin Kutsche","doi":"10.1007/s10048-023-00716-w","DOIUrl":"10.1007/s10048-023-00716-w","url":null,"abstract":"<p><p>DNM1 developmental and epileptic encephalopathy (DEE) is characterized by severe to profound intellectual disability, hypotonia, movement disorder, and refractory epilepsy, typically presenting with infantile spasms. Most of the affected individuals had de novo missense variants in DNM1. DNM1 undergoes alternative splicing that results in expression of six different transcript variants. One alternatively spliced region affects the tandemly arranged exons 10a and 10b, producing isoforms DNM1A and DNM1B, respectively. Pathogenic variants in the DNM1 coding region affect all transcript variants. Recently, a de novo DNM1 NM_001288739.1:c.1197-8G > A variant located in intron 9 has been reported in several unrelated individuals with DEE that causes in-frame insertion of two amino acids and leads to disease through a dominant-negative mechanism. We report on a patient with DEE and a de novo DNM1 variant NM_001288739.2:c.1197-46C > G in intron 9, upstream of exon 10a. By RT-PCR and Sanger sequencing using fibroblast-derived cDNA of the patient, we identified aberrantly spliced DNM1 mRNAs with exon 9 spliced to the last 45 nucleotides of intron 9 followed by exon 10a (NM_001288739.2:r.1196_1197ins[1197-1_1197-45]). The encoded DNM1A mutant is predicted to contain 15 novel amino acids between Ile398 and Arg399 [NP_001275668.1:p.(Ile398_Arg399ins15)] and likely functions in a dominant-negative manner, similar to other DNM1 mutants. Our data confirm the importance of the DNM1 isoform A for normal human brain function that is underscored by previously reported predominant expression of DMN1A transcripts in pediatric brain, functional differences of the mouse Dnm1a and Dnm1b isoforms, and the Dnm1 fitful mouse, an epilepsy mouse model.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 3","pages":"171-180"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10149054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COLQ-related congenital myasthenic syndrome: An integrative view.","authors":"Tina Eshaghian,&nbsp;Bahareh Rabbani,&nbsp;Reza Shervin Badv,&nbsp;Sahar Mikaeeli,&nbsp;Behdad Gharib,&nbsp;Stanley Iyadurai,&nbsp;Nejat Mahdieh","doi":"10.1007/s10048-023-00719-7","DOIUrl":"10.1007/s10048-023-00719-7","url":null,"abstract":"<p><p>Congenital myasthenic syndromes are inherited disorders caused by mutation in components of the neuromuscular junction and manifest early in life. Mutations in COLQ gene result in congenital myasthenic syndrome. Here, we present the analysis of data from 209 patients from 195 unrelated families highlighting genotype-phenotype correlation. In addition, we describe a COLQ homozygous variant a new patient and discuss it utilizing the Phyre2 and I-TASSER programs. Clinical, molecular genetics, imaging (MRI), and electrodiagnostic (EEG, EMG/NCS) evaluations were performed. Our data showed 89 pathogenic/likely pathogenic variants including 35 missenses, 21 indels, 14 nonsense, 14 splicing, and 5 large deletions variants. Eight common variants were responsible for 48.46% of those. Weakness in proximal muscles, hypotonia, and generalized weakness were detected in all individuals tested. Apart from the weakness, extensive clinical heterogeneity was noted among patients with COLQ-related patients based on their genotypes-those with variants affecting the splice site exhibited more severe clinical features while those with missense variants displayed milder phenotypes, suggesting the role of differential splice variants in multiple functions within the muscle. Analyses and descriptions of these COLQ variants may be helpful in clinical trial readiness and potential development of novel therapies in the setting of established structure-function relationships.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 3","pages":"189-200"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9793818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to a letter to the editor.","authors":"Jeanne Jury,&nbsp;Mathilde Nizon,&nbsp;Benjamin Cogné,&nbsp;Bertrand Isidor","doi":"10.1007/s10048-023-00721-z","DOIUrl":"10.1007/s10048-023-00721-z","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 3","pages":"219"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cohen syndrome and early-onset epileptic encephalopathy in male triplets: two disease-causing mutations in VPS13B and NAPB.","authors":"Alice AbdelAleem,&nbsp;Naim Haddad,&nbsp;Ghada Al-Ettribi,&nbsp;Amy Crunk,&nbsp;Ahmed Elsotouhy","doi":"10.1007/s10048-023-00710-2","DOIUrl":"https://doi.org/10.1007/s10048-023-00710-2","url":null,"abstract":"<p><p>Cohen syndrome (CS) is a rare multisystem autosomal recessive disorder associated with mutations in VPS13B (vacuolar protein sorting homolog 13B). The NAPB-related neurodevelopmental disorder is characterized mainly by early-onset epileptic encephalopathy (EOEE) and is associated with mutations in NAPB that encodes for SNAP-beta (soluble NSF attachment protein beta). Here we describe male triplets, clinically presenting with the phenotype of subtle but distinctive facial features, intellectual disability, increased body weight, neonatal EOEE, and prominently variable abnormal behaviors of autism and sexual arousal. The EEG showed multifocal epilepsy, while the brain MRI showed no abnormalities. Diagnostic exome sequencing (ES), the applied next-generation sequencing approach, revealed the interesting finding of two novel homozygous variants in two genes: VPS13B missense variant (c.8516G > A) and NAPB splice-site loss (c.354 + 2 T > G). Sanger sequencing verified the segregation of the two recessive gene variants with the phenotype in family members. The prediction algorithms support the pathogenicity of these variants. Homozygosity mapping of ES data of this consanguineous family revealed multiple chromosomal regions of homozygosity stretches with the residing of VPS13B (chr8: 100830758G > A) and NAPB (Chr20: 23,375,774 A > C) variants within the largest homozygous blocks further supporting the disease-genes causal role. Interestingly, the functions of the two proteins; VPS13B, a transmembrane protein involved in intracellular protein transport, and SNAP-beta involved in neurotransmitters release at the neuronal synaptic complexes, have been associated with Golgi-mediated vesicular trafficking. Our ES findings provide new insights into the pathologic mechanism underlying the expansion of the neurodevelopmental spectrum in CS and further highlight the importance of Golgi and Golgi-membrane-related proteins in the development of neurodevelopmental syndromes associated with early-onset non-channelopathy epilepsy. To our knowledge, this is the first report documenting multifocal EOEE in CS patients with the association of a pathogenic NAPB variant.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"103-112"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9285065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodegeneration with brain iron accumulation: a case series highlighting phenotypic and genotypic diversity in 20 Indian families.","authors":"Haseena Sait,&nbsp;Somya Srivastava,&nbsp;Manmohan Pandey,&nbsp;Deepak Ravichandran,&nbsp;Anju Shukla,&nbsp;Kausik Mandal,&nbsp;Deepti Saxena,&nbsp;Arya Shambhavi,&nbsp;Purvi Majethia,&nbsp;Lakshmi Priya Rao,&nbsp;Suvasini Sharma,&nbsp;Shubha R Phadke,&nbsp;Amita Moirangthem","doi":"10.1007/s10048-023-00712-0","DOIUrl":"https://doi.org/10.1007/s10048-023-00712-0","url":null,"abstract":"<p><p>Neurodegeneration with brain iron accumulation (NBIA) is an umbrella term encompassing various inherited neurological disorders characterised by abnormal iron accumulation in basal ganglia. We aimed to study the clinical, radiological and molecular spectrum of disorders with NBIA. All molecular-proven cases of NBIA presented in the last 5 years at 2 tertiary care genetic centres were compiled. Demographic details and clinical and neuroimaging findings were collated. We describe 27 individuals from 20 unrelated Indian families with causative variants in 5 NBIA-associated genes. PLA2G6-associated neurodegeneration (PLAN) was the most common, observed in 13 individuals from 9 families. They mainly presented in infancy with neuroregression and hypotonia. A recurrent pathogenic variant in COASY was observed in two neonates with prenatal-onset severe neurodegeneration. Pathogenic bi-allelic variants in PANK2, FA2H and C19ORF12 genes were observed in the rest, and these individuals presented in late childhood and adolescence with gait abnormalities and extrapyramidal symptoms. No intrafamilial and interfamilial variability were observed. Iron deposition on neuroimaging was seen in only 6/17 (35.3%) patients. A total of 22 causative variants across 5 genes were detected including a multiexonic duplication in PLA2G6. The variants c.1799G > A and c.2370 T > G in PLA2G6 were observed in three unrelated families. In silico assessments of 8 amongst 9 novel variants were also performed. We present a comprehensive compilation of the phenotypic and genotypic spectrum of various subtypes of NBIA from the Indian subcontinent. Clinical presentation of NBIAs is varied and not restricted to extrapyramidal symptoms or iron accumulation on neuroimaging.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"113-127"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9344825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two patients with KDM3B variants and new presentations of Diets-Jongmans syndrome.","authors":"Xiangyue Zhao,&nbsp;Tingting Yu,&nbsp;Jie Tang,&nbsp;Ru-En Yao,&nbsp;Niu Li,&nbsp;Jian Wang","doi":"10.1007/s10048-023-00711-1","DOIUrl":"https://doi.org/10.1007/s10048-023-00711-1","url":null,"abstract":"<p><p>KDM3B is located on chromosome 5q31 and encodes KDM3B, which is involved in histone demethylation and epigenetic regulation. Pathogenic KDM3B variants cause a dominantly inherited disorder presenting with intellectual disability (ID), short stature, and facial dysmorphism, named Diets-Jongmans syndrome. We describe two patients with KDM3B variants presenting with Diets-Jongmans syndrome. Genetic testing was performed because of the clinical data and a lack of a clear diagnosis in both patients. Candidate variants were verified by Sanger sequencing. After KDM3B variants were detected, in silico tools were used to predict the pathogenicity of the missense variants. A minigene assay was performed to evaluate the splicing effects of the c.5070 + 1G > A variant on KDM3B. Patient 1 mainly presented with repetitive upper respiratory tract infection and patient 2 presented with palpitation, shortness of breath, and pitting edema; both had ID. Whole exome sequencing identified variants of KDM3B. Patient 1 had the de novo KDM3B c.5070 + 1G > A variant, whereas patient 2 had the c.2828G > A (p.R943Q) variant. Transcriptional experiments of the splicing variant c.5070 + 1G > A revealed aberrant transcripts leading to truncated protein products. We found two pathogenic variants in KDM3B, one of which is novel. Both patients had additional clinical presentations, and patient 1 had transient neutropenia. KDM3B c.5070 + 1G > A is the first KDM3B splice-site variant and was identified as a germline variant. Neutropenia and cardiomyopathy are newly found presentations of Diets-Jongmans syndrome. Our report enriches our knowledge of the genotypic spectrum of the KDM3B variants and phenotypic diversity of Diets-Jongmans syndrome.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"95-101"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9291057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}