European Journal of Human Genetics最新文献

{"title":"Biallelic and monoallelic variants in EFEMP1 can cause a severe and distinct subtype of heritable connective tissue disorder.","authors":"M O Mol, T J van Ham, N Bannink, H T Bruggenwirth, J C Escher, J M Kros, J J M Renkens, L van Unen, R M Verdijk, J Vlot, V J M Verhoeven, S Demirdas","doi":"10.1038/s41431-024-01692-x","DOIUrl":"https://doi.org/10.1038/s41431-024-01692-x","url":null,"abstract":"<p><p>Variants in EFEMP1, encoding Fibulin-3, were previously reported as a rare cause of heritable connective tissue disorder (HCTD) with recurrent hernias and joint hypermobility. We report three new cases with biallelic or monoallelic EFEMP1 variants and severe hernia phenotypes. Two male siblings of 10 and 13 years old presented with marfanoid habitus, recurrent inguinal and umbilical hernias, generalized joint hypermobility, and scoliosis. Parents and halfsiblings reported joint hypermobility and umbilical hernias. The eldest boy died at age 16 from incarcerated gastrointestinal herniation complicated by gastric and bowel necrosis with perforation. Autopsy revealed widespread intestinal diverticula. Immunohistochemistry of skin and fascia tissue did not reveal any abnormalities, including normal staining of elastic fibers. Both siblings harbored compound heterozygous likely pathogenic EFEMP1 variants (c.1320 + 2T > A, p.? and c.698G > A, p.Gly233Asp). An unrelated 58-year-old male had marfanoid features, high myopia, recurrent diaphragmatic and inguinal hernias, and chronic gastrointestinal dilatation with severe malabsorption. Both his dizygotic twin-brother and mother had recurrent hernias and high myopia. This man died at 59 years of age, and autopsy showed extensive diaphragmatic herniation, bowel diverticula, and pulmonary emphysema. A heterozygous EFEMP1 splice-variant (c.81 + 1G > A, p.?) was identified, causing exon skipping leading to a start-loss. Targeted genome reanalysis nor RNA-sequencing revealed a second variant at the other allele. The reported individuals expand the clinical and pathological phenotypes of EFEMP1-related disease, a distinct entity within the spectrum of HCTD. The severe and recurrent hernias, gastrointestinal dilatation, and diverticulosis result in an increased risk for life-threatening complications, demanding early recognition and close monitoring.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equity and timeliness as factors in the effectiveness of an ethical prenatal sequencing service: reflections from parents and professionals.","authors":"Michelle Peter, Melissa Hill, Jane Fisher, Morgan Daniel, Hannah McInnes-Dean, Rhiannon Mellis, Holly Walton, Caroline Lafarge, Kerry Leeson-Beevers, Sophie Peet, Dagmar Tapon, Sarah L Wynn, Lyn S Chitty, Michael Parker","doi":"10.1038/s41431-024-01700-0","DOIUrl":"https://doi.org/10.1038/s41431-024-01700-0","url":null,"abstract":"<p><p>Prenatal sequencing tests are being introduced into clinical practice in many developed countries. In part due to its greater ability to detect genetic variation, offering prenatal sequencing can present ethical challenges. Here we review ethical issues arising following the implementation of prenatal sequencing in the English National Health Service (NHS). We analysed semi structured interviews conducted with 48 parents offered prenatal sequencing and 63 health professionals involved in delivering the service to identify the ethical issues raised. Two main themes were identified: (1) Equity of access (including issues around eligibility criteria, laboratory analytical processes, awareness and education of clinicians, fear of litigation, geography, parental travel costs, and access to private healthcare), and (2) Timeliness and its impact on parental decision-making in pregnancy (in the context of the law around termination of pregnancy, decision-making in the absence of prenatal sequencing results, and the \"importance\" of prenatal sequencing results). Recognising both the practical and systemic ethical issues that arise out of delivering a national prenatal sequencing service is crucial. Although specific to the English context, many of the issues we identified are applicable to prenatal sequencing services more broadly. Education of health professionals and parents will help to mitigate some of these ethical issues.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining the complex needs of families with rare diseases-the example of telomere biology disorders.","authors":"Catherine Wilsnack, Camella J Rising, Emily E Pearce, Rowan Forbes Shepherd, Ashley S Thompson, Alina Majid, Allison Werner-Lin, Sharon A Savage, Sadie P Hutson","doi":"10.1038/s41431-024-01697-6","DOIUrl":"https://doi.org/10.1038/s41431-024-01697-6","url":null,"abstract":"<p><p>Families with rare diseases, such as telomere biology disorders (TBDs), may have extensive unmet needs given the heterogeneity, chronicity, and potential severity of illness. TBDs are rare inherited syndromes associated with high risk of bone marrow failure, cancer, pulmonary fibrosis, and other severe, chronic complications. To identify gaps in clinical care, we aimed to ascertain the perceived unmet needs of adults and family caregivers, current or bereaved, of individuals with TBDs. Participants were aged ≥18 years with a self-reported TBD diagnosis and/or ever caregivers to one or more family members with a TBD. Participants completed an online survey (N = 35) and/or an audio-recorded telephone interview (N = 32). We calculated descriptive statistics in SPSS and thematically analyzed interview transcripts. Quantitative and qualitative data were analyzed concurrently. Most participants were aged ≥35 years, female, highly educated, and medically insured. Survey respondents reported numerous unmet needs in psychosocial, medical, financial, and daily activity domains. In interviews, participant descriptions validated and contextualized the salience of these unmet needs. Both qualitative and quantitative data identified critical shortfalls in addressing chronic family distress and specialty care coordination. Adults and caregivers of individuals with TBDs have a high risk of adverse psychosocial sequelae given extensive unmet needs. These findings provide a foundation for understanding the range and extent of gaps in care for families with rare diseases, especially TBDs but that are likely applicable to others. Tailored multi-disciplinary interventions involving patients, families, clinicians, researchers, and patient advocacy communities are required to appropriately address care needs for all rare diseases.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guiding the future of clinical care and clinical research in Birt-Hogg-Dubé.","authors":"Michel Alchoueiry, W Clark Lambert, Elizabeth P Henske","doi":"10.1038/s41431-024-01696-7","DOIUrl":"https://doi.org/10.1038/s41431-024-01696-7","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosome segregation of human nonhomologous Robertsonian translocations: insights from preimplantation genetic testing.","authors":"Peter Benn, Katrina Merrion","doi":"10.1038/s41431-024-01693-w","DOIUrl":"https://doi.org/10.1038/s41431-024-01693-w","url":null,"abstract":"<p><p>Robertsonian translocations (robs) are associated with a high risk for unbalanced segregations. Preimplantation Genetic Testing (PGT) offers an early opportunity to evaluate segregation patterns and selection against chromosome imbalances. The objective of this study was to evaluate the chromosome complements in blastocysts for male and female rob carriers and provide information useful in PGT counseling for rob carriers. PGT results were reviewed for 296 couples where a balanced and nonhomologous rob was present in one member of the couple. All embryos had day 5/6 trophectoderm biopsy and SNP-based PGT. The study included 2235 blastocysts, of which 2151 (96.2%) had results. Significantly fewer blastocysts were available for female rob carriers (mean 4.60/IVF cycle) compared to males (5.49/cycle). Male carriers were more likely to have blastocysts with a normal/balanced chromosome complement; 84.8% versus 62.8% (P < 0.00001). Male carriers had fewer blastocysts with monosomy (60/152, 39.5%) compared to female carriers (218/396, 55.1%) (P = 0.001). Twenty-one (1%) blastocysts showed 3:0 segregation; these were mostly double trisomies and derived from female carriers. Differences between chromosome complements for male versus female carriers suggest that selection against unbalanced forms may occur during spermatogenesis. Six blastocyst samples showed an unexpected (\"noncanonical\") combination of trisomy and monosomy. One case of uniparental disomy was identified. For female carriers, there was no association between unbalanced segregation and parental age but for male carriers, there was an inverse association. PGT is a highly beneficial option for rob carriers and patients can be counseled using our estimates for the chance of at least one normal/balanced embryo.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel variants in the SOX11 gene: clinical description of seven new patients.","authors":"Beatriz Schincariol-Manhe, Érica Campagnolo, Samira Spineli-Silva, Nicole de Leeuw, Gabriela Roldão Correia-Costa, André Pessoa, Carolina Fischinger Moura de Souza, Cathy Stevens, Poupak Javaher, Helena Fabbri Scallet, Julia Mohr, Saskia Biskup, Johanna C Herkert, Rolph Pfundt, Lakshmi Mehta, Aisha Rekab, Houda Zghal Elloumi, May Sanyoura, Andréa Trevas Maciel-Guerra, Vera Lúcia Gil-da-Silva-Lopes, Ana Mondadori Dos Santos, Társis Paiva Vieira","doi":"10.1038/s41431-024-01695-8","DOIUrl":"https://doi.org/10.1038/s41431-024-01695-8","url":null,"abstract":"<p><p>Pathogenic SOX11 variants have been associated with intellectual developmental disorder with microcephaly, and with or without ocular malformations or hypogonadotropic hypogonadism (HH) (IDDMOH, OMIM # 615866). In this article, we report seven new patients with de novo SOX11 variants. Five of the variants are missense, one nonsense, and one whole-gene deletion, most of them are novel variants. The main clinical features included neurodevelopmental delay (7/7) and intellectual disability (5/7), autism/attention deficit hyperactivity disorder (5/7), microcephaly (4/7), short stature (4/7), hypotonia (4/7), and clinodactyly of the 5th fingers (5/7). HH was confirmed in two female patients with primary amenorrhea, nonvisualized/prepubertal size of the uterus, and nonvisualized ovaries. Two of the male patients presented with micropenis, two had cryptorchidism, and one had decreased testicular size, which are suggestive findings of HH. This article contributes to the clinical characterization of patients with SOX11 variants and supports the role of this gene in HH.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering recessive alleles in rare Mendelian disorders by genome sequencing of 174 individuals with monoallelic pathogenic variants.","authors":"Gaby Schobers, Maartje Pennings, Juliette de Vries, Michael Kwint, Jeroen van Reeuwijk, Jordi Corominas Galbany, Ronald van Beek, Eveline Kamping, Raoul Timmermans, Erik-Jan Kamsteeg, Lonneke Haer-Wigman, Frans P M Cremers, Susanne Roosing, Christian Gilissen, Hannie Kremer, Han G Brunner, Helger G Yntema, Lisenka E L M Vissers","doi":"10.1038/s41431-024-01694-9","DOIUrl":"https://doi.org/10.1038/s41431-024-01694-9","url":null,"abstract":"<p><p>Clinical exome sequencing (ES) has facilitated genetic diagnosis in individuals with a rare genetic disorder by analysis of all protein-coding sequences in a single experiment. However, in 40-60% of patients, a conclusive diagnosis remains elusive. In 2-5% of these individuals, ES does identify a disease-associated monoallelic variant in a recessive disorder. We hypothesized that short-read genome sequencing (GS) might uncover a pathogenic variant on the second allele, thereby increasing diagnostic yield. We performed GS for 174 individuals in whom ES identified a monoallelic pathogenic variant in a gene associated with recessive disease related to their phenotype. GS interpretation was limited to the (non-)coding parts of the gene in which this first pathogenic variant was identified, focusing on splice-disrupting variants. Firstly, we uncovered a second pathogenic variant affecting coding sequence in five individuals, including two SNV/indel variants, two copy number variants, and one insertion. Secondly, for 24 individuals, we identified a total of 31 rare non-coding intronic SNV/indel variants, all predicted to disrupt splicing. Using functional follow-up assays, we confirmed an effect on splicing for three of these variants (in ABCA4, POLR3A and COL4A4) in three individuals. In summary, we identified a (likely) pathogenic second variant in 4.6% (8/174), and a possible diagnosis for 12.1% (21/174) of our cohort. Hence, when performing GS as first-tier diagnostic test, including the interpretation of SVs and rare intronic variants in known recessive disease genes, the overall diagnostic yield of rare disease will increase. The added diagnostic value of GS for recessive disease In our cohort of 174 individuals (84 males and 90 females) with a monoallelic pathogenic variant in genes associated with a wide and diverse range of recessive diseases (pie chart), using genome sequencing (GS) and a systematic approach (methods), we identified eight new diagnoses (4.6%). We identified a second likely pathogenic variant in eight individuals (results); In two a second coding variant was found, in three others, a rare non-coding SNV anticipated to disrupt splicing was uncovered, and in three individuals a structural rearrangement was identified (two copy number variants (CNV), and one structural variant (SV)).</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype-driven genomics enhance diagnosis in children with unresolved neuromuscular diseases.","authors":"Berta Estévez-Arias, Leslie Matalonga, Delia Yubero, Kiran Polavarapu, Anna Codina, Carlos Ortez, Laura Carrera-García, Jesica Expósito-Escudero, Cristina Jou, Stefanie Meyer, Ozge Aksel Kilicarslan, Alberto Aleman, Rachel Thompson, Rebeka Luknárová, Anna Esteve-Codina, Marta Gut, Steven Laurie, German Demidov, Vicente A Yépez, Sergi Beltran, Julien Gagneur, Ana Topf, Hanns Lochmüller, Andres Nascimento, Janet Hoenicka, Francesc Palau, Daniel Natera-de Benito","doi":"10.1038/s41431-024-01699-4","DOIUrl":"https://doi.org/10.1038/s41431-024-01699-4","url":null,"abstract":"<p><p>Establishing a molecular diagnosis remains challenging in half of individuals with childhood-onset neuromuscular diseases (NMDs) despite exome sequencing. This study evaluates the diagnostic utility of combining genomic approaches in undiagnosed NMD patients. We performed deep phenotyping of 58 individuals with unsolved childhood-onset NMDs that have previously undergone inconclusive exome studies. Genomic approaches included trio genome sequencing and RNASeq. Genetic diagnoses were reached in 23 out of 58 individuals (40%). Twenty-one individuals carried causal single nucleotide variants (SNVs) or small insertions and deletions, while 2 carried pathogenic structural variants (SVs). Genomic sequencing identified pathogenic variants in coding regions or at the splice site in 17 out of 21 resolved cases, while RNA sequencing was additionally required for the diagnosis of 4 cases. Reasons for previous diagnostic failures included low coverage in exonic regions harboring the second pathogenic variant and involvement of genes that were not yet linked to human diseases at the time of the first NGS analysis. In summary, our systematic genetic analysis, integrating deep phenotyping, trio genome sequencing and RNASeq, proved effective in diagnosing unsolved childhood-onset NMDs. This approach holds promise for similar cohorts, offering potential improvements in diagnostic rates and clinical management of individuals with NMDs.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin assembly factor subunit CHAF1A as a monogenic cause for oculo-auriculo-vertebral spectrum.","authors":"Véronique Pingault, Cécilia Neiva-Vaz, Judite de Oliveira, Núria Martínez-Gil, Amaia Lasa-Aranzasti, Berta Campos, Inge M M Lakeman, Esther A R Nibbeling, Radka Stoeva, Parul Jayakar, Tabib Dabir, Houda Zghal Elloumi, Alanna Strong, Sylvain Hanein, Arnaud Picard, Francoise Ochsenbein, Pierre Blanc, Jeanne Amiel","doi":"10.1038/s41431-024-01698-5","DOIUrl":"https://doi.org/10.1038/s41431-024-01698-5","url":null,"abstract":"<p><p>Oculo-auriculo-vertebral spectrum (OAVS) is characterized by abnormal development of the 1st and 2nd branchial arches. Despite arguments against a monogenic condition, a few genes have been involved in a minority of cases. We now report heterozygous, presumably loss-of function variants in the CHAF1A gene in 8 individuals, including 3 members of the same family. Four cases fulfill stringent diagnostic criteria for OAVS, including asymmetric ear dysplasia, preauricular tags, mandibular asymmetry +/- vertebral malformations. Two patients also presented with kidney malformations. CHAF1A encodes a subunit of CAF-1 (chromatin assembly factor-1), a heterotrimeric protein complex responsible for the deposition of newly synthesized histones H3-H4 onto the newly synthetized DNA strand during replication. The identification of loss-of-unction variants in CHAF1A is consistent with the hypothesis of early developmental genes dysregulation driving OAVS and other associations recently lumped under the acronym Recurrent Constellations of Embryonic Malformations (RCEM).</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insight into the genotype-phenotype correlation of PTH1R variants and primary failure of tooth eruption on an Italian Cohort.","authors":"Clarissa Modafferi, Elisabetta Tabolacci, Filomena Lo Vecchio, Ilaria Cassano, Roberto Bertozzi, Arcangelo Fargnoli, Concetta Cafiero, Ettore Lo Cascio, Alessandro Arcovito, Cristina Grippaudo, Pietro Chiurazzi","doi":"10.1038/s41431-024-01691-y","DOIUrl":"https://doi.org/10.1038/s41431-024-01691-y","url":null,"abstract":"<p><p>Primary failure of tooth eruption (PFE) is an autosomal dominant disease with penetrance defect. While the clinical phenotype is relatively well-defined since the 70 s of the last centuries, much more need to be clarified about the genetic causes of this condition. In our previous paper we established clinical criteria to better identify PFE patients carrying PTH1R gene variants. We examined a new cohort of 32 patients, including one or more relatives for 7 patients (43 cases in total), referred to have PFE and recruited from our Hospital and from external outpatients. Sequencing analysis of the PTH1R coding sequence in this cohort of patients revealed 9 different variants, 4 exonic and 5 intronic. Through in silico prediction tools and databases, 3 of them (2 exonic and 1 in a splicing site) had been considered potentially involved in the PFE phenotype. Sequencing of cDNA was unsuccessfully attempted due to the low levels of PTH1R expression in the analysed tissues. The yield of the genetic test increases when the clinical selection of the patients with dental eruption failure is well-characterized. Dental eruption failure with pure clinical findings of PFE associated with familial history revealed variants in PTH1R gene, offering a diagnostic test for the family. Characterization of novel variants in the most relevant responsible gene of the PFE could bring to a more accurate diagnosis and therapeutic approach in the future and to a deeper comprehension of the disease.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}