phenotypes

表型
  • 文章类型: Journal Article
    引言CEP152编码蛋白Cep152,其与中心体功能相关。缺少Cep152会导致中心体重复失败。CEP152发生变异,引起多种疾病,如Seckel综合征-5和原发性小脑-9。方法在本研究中,我们报告了在天津市儿童医院诊断为癫痫的患者。我们进行了临床检查和实验室检查,并对先证者及其父母的外周血进行全外显子组测序。通过Sanger测序和定量实时聚合酶链反应技术验证了CEP152基因中可疑的复合杂合变体。结果我们发现了三种变体,其中两种来自CEP152,一种来自HPD。结果显示仅在CEP152中的变体。患者经常出现癫痫发作。Sanger测序显示CEP152中的两个新变体位于外显子26(NM_014985.3c.3968C>Ap.Ser1323*)和外显子16(NM_014985.3c.2034_2036delp.Tyr678*)。结论本研究中我们报道了CEP152基因中的一个新的复合杂合变体。大多数表型是塞克尔综合征和原发性小脑,这种新的变异可能会导致一种非典型的癫痫表型。
    Introduction   CEP152 encodes protein Cep152, which associates with centrosome function. The lack of Cep152 can cause centrosome duplication to fail. CEP152 mutates, causing several diseases such as Seckel syndrome-5 and primary microencephaly-9. Methods  In this study, we reported a patient diagnosed with epilepsy in Tianjin Children\'s Hospital. We performed clinical examination and laboratory test, and whole-exome sequencing was performed for the proband\'s and his parents\' peripheral blood. The suspected compound-heterozygous variant in the CEP152 gene was verified by Sanger sequencing and quantitative real-time polymerase chain reaction technology. Results  We discovered three variants-two of them from CEP152 and one from HPD . The result showed the variants in CEP152 only. The patient presented with seizures frequently. Sanger sequencing showed two novel variants in CEP152 are in exon26 (NM_014985.3 c.3968C > A p.Ser1323*) and in exon16 (NM_014985.3 c.2034_2036del p.Tyr678*). Conclusions  We reported a novel compound-heterozygous variant in the CEP152 gene in this study. Most of the phenotypes are Seckel syndrome and primary microencephaly, and the novel variant may cause an atypical phenotype that is epilepsy.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    这项观察性病例对照研究分析了临床,功能,炎症谱,以及在教学医院门诊随访的哮喘患者队列的治疗数据。在2008年1月至2020年2月期间访问诊所并根据全球哮喘倡议(GINA)标准诊断为哮喘的患者被纳入研究。患者大致分为两组:年龄<60岁或年龄≥60岁。评估患者的哮喘控制和严重程度,使用的药物,合并症,吸烟状况,恶化的发生,第一次和最后一次访问时的肺活量测定,痰细胞学,过敏性刺痛试验,和炎性细胞因子水平。60岁以上患者的哮喘控制测试(ACT)评分较低,需要更高剂量的吸入性糖皮质激素来实现哮喘控制,并且在固定气道阻塞的情况下肺功能更差,更多的合并症,更多的烟草接触,与年轻的哮喘患者相比,门诊随访时间更长。此外,与年轻患者相比,老年患者出现中性粒细胞增多症,诱导痰中TNFα水平较高.这些结果表明,年龄≥60岁的哮喘患者比年轻的哮喘患者有更严重的哮喘症状和更差的肺功能。此外,老化,长期哮喘,合并症,烟草暴露导致肺功能加速下降。
    ObjectiveThis observational case-control study analyzed the clinical, functional, inflammatory profile, and treatment data of a cohort of patients with asthma who were followed up at the outpatient clinic of a teaching hospital.MethodsPatients who visited the clinic between January 2008 and February 2020 and diagnosed with asthma according to the Global Initiative for Asthma (GINA) criteria were included in the study. Patients were broadly classified into two groups: age <60 or age ≥60 years. The patients were evaluated for asthma control and severity, medications used, comorbidities, smoking status, occurrence of exacerbation, spirometry at the first and last visits, sputum cytology, allergic prick test, and inflammatory cytokine levels.ResultsPatients over 60 years of age had lower asthma control test (ACT) scores, required higher doses of inhaled corticosteroids to achieve asthma control and had worse lung function with fixed airway obstruction, higher number of comorbidities, greater exposure to tobacco, and longer outpatient follow-up than younger patients with asthma. Furthermore, older patients presented with neutrophilia and higher levels of TNFα in the induced sputum as compared to younger patients.ConclusionsThese findings suggest that patients aged ≥60 years of age had a more severe asthma profile and poorer lung function than younger patients with asthma. Furthermore, aging, long-term asthma, comorbidities, and tobacco exposure contributed to an accelerated decline in lung function.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Case Reports
    分析13例产前诊断为Joubert综合征(JS)的产前影像学表型和基因型,所有这些都接受了磁共振成像(MRI),超声,和基因检测。产前MRI诊断为JS10例,具有典型的磨牙征(MTS),而产前超声诊断或可疑诊断为JS的11例,有典型或轻度MTS的10例。10例发现JS相关基因突变和其他产前JS影像学表型,包括两种情况下的OFD1[小脑疣(CV)缺失,后颅窝扩张,脑室肿大,多指,皮质发育(MCD)畸形,和持续的左上腔静脉],两种情况下的TMEM67(CV缺失,多指,高回声肾或多囊肾,后颅窝扩张,和脑室肿大),两种情况下的CC2D2A(CV缺失,多指,MCD,call体的发育不全,脑膨出和脑积水,脑室肿大,和后颅窝扩张),RPGRIP1L在一种情况下(CV缺失),一种情况下的TCTN3(CV缺失,多指,MCD,和后颅窝扩张),CEP2901例(CV缺失和多囊肾),和NPHP1在一种情况下(CV缺失)。JS的产前诊断提出了许多挑战,包括未知意义的变异,产前成像中缺乏功能评估,在产前评估中不清楚表型-基因型关系,以及对JS标志的不正确识别,MTS,在产前成像中,尤其是超声波。虽然联合MRI,超声,外显子组测序有助于提高JS的产前诊断,仍然存在重大挑战。
    Prenatal imaging phenotypes and genotypes were analyzed in 13 cases prenatally diagnosed with Joubert syndrome (JS), all of which underwent magnetic resonance imaging (MRI), ultrasound, and genetic testing. Prenatal MRI diagnosed 10 cases as JS with a typical molar tooth sign (MTS), while prenatal ultrasound diagnosed or suspiciously diagnosed 11 cases as JS with typical or mild MTS in 10 cases. Mutations in JS-related genes and other prenatal JS imaging phenotypes were identified in 10 cases, including OFD1 in two cases [cerebellar vermis (CV) absence, posterior fossa dilation, ventriculomegaly, polydactyly, malformations of cortical development (MCD), and persistent left superior vena cava], TMEM67 in two cases (CV absence, polydactyly, hyperechoic kidneys or polycystic kidneys, posterior fossa dilation, and ventriculomegaly), CC2D2A in two cases (CV absence, polydactyly, MCD, agenesis of the corpus callosum, encephalocele and hydrocephalus, ventriculomegaly, and posterior fossa dilation), RPGRIP1L in one case (CV absence), TCTN3 in one case (CV absence, polydactyly, MCD, and posterior fossa dilation), CEP290 in one case (CV absence and polycystic kidney), and NPHP1 in one case (CV absence). The prenatal diagnosis of JS presents a number of challenges, including the variants of unknown significance, the lack of functional assessment in prenatal imaging, unclear phenotype-genotype relationships in prenatal evaluation, and the incorrect identification of the JS hallmark, the MTS, in prenatal imaging, especially on ultrasound. Although combined MRI, ultrasound, and exome sequencing could help improve the prenatal diagnosis of JS, there still exist significant challenges.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Case Reports
    背景:多基因风险评分(PRS)已广泛应用于研究中,显示了如何将人口群体分层为许多常见条件的风险类别。随着医疗保健系统考虑应用PRS来保持人口健康,在个人层面上展示其实施的工作很少。
    方法:我们对已建立的数据存储库的PRS源进行了系统的管理,选择15个表型,包括超过3700万个与癌症相关的SNP,心血管,代谢和自身免疫性疾病。我们使用全基因组测序数据测试了四个相关个体的家族的选定表型。基于1000个伊比利亚人基因组中的参考分布,给出了个体风险评分的百分位值,欧洲人,或所有样品。计算了超过960亿个等位基因效应,以获得此处分析的每个个体的PRS。
    结论:我们的研究结果强调了在开发和共享PRS的方式上进一步标准化的必要性。个人风险评估的重要性,而不是继承平均值的假设,以及将PRS转化为风险指标时当前面临的挑战。
    BACKGROUND: Polygenic risk scores (PRS) have been widely applied in research studies, showing how population groups can be stratified into risk categories for many common conditions. As healthcare systems consider applying PRS to keep their populations healthy, little work has been carried out demonstrating their implementation at an individual level.
    METHODS: We performed a systematic curation of PRS sources from established data repositories, selecting 15 phenotypes, comprising an excess of 37 million SNPs related to cancer, cardiovascular, metabolic and autoimmune diseases. We tested selected phenotypes using whole genome sequencing data for a family of four related individuals. Individual risk scores were given percentile values based upon reference distributions among 1000 Genomes Iberians, Europeans, or all samples. Over 96 billion allele effects were calculated in order to obtain the PRS for each of the individuals analysed here.
    CONCLUSIONS: Our results highlight the need for further standardisation in the way PRS are developed and shared, the importance of individual risk assessment rather than the assumption of inherited averages, and the challenges currently posed when translating PRS into risk metrics.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    自闭症谱系障碍(ASD)症状儿童的异质性使其难以识别危险因素和有效的治疗方案。我们试图确定行为和发育特征,以最好地定义具有ASD和亚阈值ASD特征的2-5岁儿童的异质性和同质性。儿童参加了ASD的多站点病例对照研究。通过母亲电话采访收集了详细的行为和发育数据,家长管理的问卷,儿童认知评估,和ASD诊断措施。具有阳性ASD筛查评分或先前ASD诊断的参与者被转介进行综合评估。根据这项评估,ASD组的儿童符合研究标准;不符合研究标准的儿童被归类为有亚阈值ASD特征。样本中有1480名被分类为ASD的儿童(81.6%的男孩)和594名被分类为具有亚阈值ASD特征的儿童(70.2%的男孩)。与失调相关的因素(例如,侵略,焦虑/抑郁,睡眠问题)其次是发育能力(例如,表达和接受语言技能)对两组儿童的异质性贡献最大。非典型的感觉反应有助于归类为ASD的儿童的同质性,而不是具有亚阈值特征的儿童。这些发现表明,失调和发育能力是临床特征,可以影响ASD和其他DD儿童的功能。在儿科记录中记录这些特征可能有助于满足个别儿童的需求。感觉功能障碍可以被认为是ASD的核心特征,因此可以用于更有针对性的筛查。评估,治疗,和研究努力。总结:自闭症谱系障碍(ASD)的多样性使得很难找到风险因素和治疗方案。我们在被分类为ASD和具有亚阈值ASD特征的儿童中确定了最不同和最相似的症状。与失调和发育能力相关的因素导致了两组儿童的多样性。感觉功能障碍是ASD儿童中最常见的症状,但不是具有亚阈值特征的儿童。研究结果可以为临床实践和研究提供信息。
    The heterogeneous nature of children with symptoms of autism spectrum disorder (ASD) makes it difficult to identify risk factors and effective treatment options. We sought to identify behavioral and developmental features that best define the heterogeneity and homogeneity in 2-5-year-old children classified with ASD and subthreshold ASD characteristics. Children were enrolled in a multisite case-control study of ASD. Detailed behavioral and developmental data were gathered by maternal telephone interview, parent-administered questionnaires, child cognitive evaluation, and ASD diagnostic measures. Participants with a positive ASD screen score or prior ASD diagnosis were referred for comprehensive evaluation. Children in the ASD group met study criteria based on this evaluation; children who did not meet study criteria were categorized as having subthreshold ASD characteristics. There were 1480 children classified as ASD (81.6% boys) and 594 children classified as having subthreshold ASD characteristics (70.2% boys) in the sample. Factors associated with dysregulation (e.g., aggression, anxiety/depression, sleep problems) followed by developmental abilities (e.g., expressive and receptive language skills) most contributed to heterogeneity in both groups of children. Atypical sensory response contributed to homogeneity in children classified as ASD but not those with subthreshold characteristics. These findings suggest that dysregulation and developmental abilities are clinical features that can impact functioning in children with ASD and other DD, and that documenting these features in pediatric records may help meet the needs of the individual child. Sensory dysfunction could be considered a core feature of ASD and thus used to inform more targeted screening, evaluation, treatment, and research efforts. LAY SUMMARY: The diverse nature of autism spectrum disorder (ASD) makes it difficult to find risk factors and treatment options. We identified the most dissimilar and most similar symptom(s) in children classified as ASD and as having subthreshold ASD characteristics. Factors associated with dysregulation and developmental abilities contributed to diversity in both groups of children. Sensory dysfunction was the most common symptom in children with ASD but not those with subthreshold characteristics. Findings can inform clinical practice and research.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Case Reports
    Currently, there is a limited understanding of long-term outcomes of COVID-19, and a need for in-home measurements of patients through the whole course of their disease. We study a novel approach for monitoring the long-term trajectories of respiratory and behavioral symptoms of COVID-19 patients at home. We use a sensor that analyzes the radio signals in the room to infer patients\' respiration, sleep and activities in a passive and contactless manner. We report the results of continuous monitoring of three residents of an assisted living facility for 3 months, through the course of their disease and subsequent recovery. In total, we collected 4,358 measurements of gait speed, 294 nights of sleep, and 3,056 h of respiration. The data shows differences in the respiration signals between asymptomatic and symptomatic patients. Longitudinally, we note sleep and motor abnormalities that persisted for months after becoming COVID negative. Our study represents a novel phenotyping of the respiratory and behavioral trajectories of COVID recovery, and suggests that the two may be integral components of the COVID-19 syndrome. It further provides a proof-of-concept that contactless passive sensors may uniquely facilitate studying detailed longitudinal outcomes of COVID-19, particularly among older adults.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    Brazil is a large country, with a population of mixed ethnic background and broad variation in dietary and physical activity traits across its five main regions. Because data on Brazilian women with polycystic ovary syndrome (PCOS) are still scarce, a nation-wide collaborative study was designed to determine the prevalence of metabolic and reproductive abnormalities and the presence of anxiety and depression in Brazilian women with PCOS. In addition, the study aims at describing how these characteristics are distributed across PCOS phenotypes and at detecting associations with regional demographic and lifestyle aspects, genetic variants, and epigenetic markers.
    The Brazilian PCOS study is being conducted in the outpatient clinics of eight university hospitals within the public healthcare network (Unified Health System) across the country. Additional centres will be included following completion of the research ethics approval process. The sample includes women with PCOS according to Rotterdam criteria at inclusion in the study and a control group of healthy women matched by age, socioeconomic status and geographical region. Data will be collected in each centre and incorporated into a unified cloud database. Clinical, demographic, socioeconomic, psychological, metabolic, epigenetic and genotypic variables will be evaluated. The data resulting from this study will be useful to guide specific public strategies for primary and secondary prevention of metabolic and reproductive comorbidities in the PCOS population of Brazil.
    The study protocol was approved by each local Research Ethics Committee. Written informed consent will be obtained from each participant. During data collection, analysis and publication, care will be taken to ensure confidentiality of participant information. Study results will be published in peer-reviewed journals and disseminated at international conferences. This research protocol was registered with the Research Ethics Committee of HCPA, through Plataforma Brasil.
    CAAE 18082413.9.1001.5327.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Sci-hub)

       PDF(Pubmed)

  • 文章类型: Case Reports
    Epilepsy caused by a KCNQ2 gene mutation usually manifests as neonatal seizures during the first week of life. The genotypes and phenotypes of KCNQ2 mutations are noteworthy.
    The KCNQ2 sequencings done were selected from 131 nonconsanguineous pediatric epileptic patients (age range: 2 days to 18 years) with nonlesional epilepsy.
    Seven (5%) index patients had verified KCNQ2 mutations: c.387+1 G>T (splicing), c.1741 C>T (p.Arg581*), c.740 C>T p.(Ser247Leu), c.853 C>A p.(Pro285Thr), c.860 C>T p.(Thr287Ile), c.1294 C>T p.(Arg432Cys), and c.1627 G>A p.(Val543Met). We found, after their paternity had been confirmed, that three patients had de novo p.(Ser247Leu), p.(Pro285Thr), and p.(Thr287Ile) mutations and neonatal-onset epileptic encephalopathy; however, their frequent seizures remitted after they turned 6 months old. Those with the c.387+1G>T (splicing), (p.Arg581*), and p.(Val543Met) mutations presented with benign familial neonatal convulsions. In addition to their relatives, 14 patients had documented KCNQ2 mutations, and 12 (86%) had neonatal seizures. The seizures of all five patients treated with oxcarbazepine remitted.
    KCNQ2-related epilepsy led to varied outcomes (from benign to severe) in our patients. KCNQ2 mutations accounted for 13% of patients with seizure onset before 2 months old in our study. KCNQ2 mutations can cause different phenotypes in children. p.(Pro 285Thr) is a novel mutation, and the p.(Pro 285Thr), p.(Ser247Leu), and p.(Thr287Ile) variants can cause neonatal-onset epileptic encephalopathy.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Sci-hub)

       PDF(Pubmed)

  • 文章类型: Journal Article
    BACKGROUND: Hypertension, obesity and diabetes are major and potentially modifiable \"risk factors\" for cardiovascular diseases. Identification of biomarkers specific to these risk factors may help understanding the underlying pathophysiological pathways, and developing individual treatment.
    METHODS: The FIBRO-TARGETS (targeting cardiac fibrosis for heart failure treatment) consortium has merged data from 12 patient cohorts in 1 common database of > 12,000 patients. Three mutually exclusive main phenotypic groups were identified (\"cases\"): (1) \"hypertensive\"; (2) \"obese\"; and (3) \"diabetic\"; age-sex matched in a 1:2 proportion with \"healthy controls\" without any of these phenotypes. Proteomic associations were studied using a biostatistical method based on LASSO and confronted with machine-learning and complex network approaches.
    RESULTS: The case:control distribution by each cardiovascular phenotype was hypertension (50:100), obesity (50:98), and diabetes (36:72). Of the 86 studied proteins, 4 were found to be independently associated with hypertension: GDF-15, LEP, SORT-1 and FABP-2; 3 with obesity: CEACAM-8, LEP and PRELP; and 4 with diabetes: GDF-15, REN, CXCL-1 and SCF. GDF-15 (hypertension + diabetes) and LEP (hypertension + obesity) are shared by 2 different phenotypes. A machine-learning approach confirmed GDF-15, LEP and SORT-1 as discriminant biomarkers for the hypertension group, and LEP plus PRELP for the obesity group. Complex network analyses provided insight on the mechanisms underlying these disease phenotypes where fibrosis may play a central role.
    CONCLUSIONS: Patients with \"mutually exclusive\" phenotypes display distinct bioprofiles that might underpin different biological pathways, potentially leading to fibrosis. Plasma protein biomarkers and their association with mutually exclusive cardiovascular phenotypes: the FIBRO-TARGETS case-control analyses. Patients with \"mutually exclusive\" phenotypes (blue: obesity, hypertension and diabetes) display distinct protein bioprofiles (green: decreased expression; red: increased expression) that might underpin different biological pathways (orange arrow), potentially leading to fibrosis.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Sci-hub)

  • 文章类型: Journal Article
    背景:本体是语义Web的关键使能技术。Web本体语言(OWL)是一种用于发布和共享本体的语义标记语言。
    目标:可定制的供应,可计算,正式代表分子遗传学信息和健康信息,通过电子健康记录(EHR)接口,可以在实现精准医疗方面发挥关键作用。在这项研究中,我们以囊性纤维化为例,构建了基于Ontology的CysticFibrobis知识库原型(OntoKBCF),通过EHR原型提供此类信息.此外,我们详细阐述了构造和表示原则,方法,应用程序,以及我们在OntoKBCF建设中面临的代表性挑战。这些原理和方法可以在构建其他基于本体的领域知识库时参考和应用。
    方法:首先,我们根据囊性纤维化在分子水平和临床表型水平上可能的临床信息需求定义了OntoKBCF的范围.然后,我们选择了要在OntoKBCF中表示的知识源。我们利用自上而下的内容分析和自下而上的构建来构建OntoKBCF。Protégé-OWL用于构建OntoKBCF。构造原则包括(1)尽可能使用现有的基本术语;(2)在表示中使用交叉和组合;(3)表示尽可能多的不同类型的事实;(4)为每种类型提供2-5个示例。Protégé-5.1.0中的HermiT1.3.8.413用于检查OntoKBCF的一致性。
    结果:成功构建了OntoKBCF,包含408个类,35个属性,和113个等效类。OntoKBCF包括原子概念(例如氨基酸)和复杂概念(例如“青春期女性囊性纤维化患者”)及其描述。我们证明了OntoKBCF可以通过EHR原型自动提供和使用可定制的分子和健康信息。主要挑战包括提供对不同患者群体的更全面的说明以及不确定知识的表示,模棱两可的概念,和负面陈述以及关于囊性纤维化的更复杂和详细的分子机制或通路信息。
    结论:虽然囊性纤维化只是一个例子,基于OntoKBCF的当前结构,扩展原型以涵盖不同主题应该相对简单。此外,支撑其发展的原则可以重复使用,用于建立替代的人类单基因疾病知识库。
    BACKGROUND: Ontologies are key enabling technologies for the Semantic Web. The Web Ontology Language (OWL) is a semantic markup language for publishing and sharing ontologies.
    OBJECTIVE: The supply of customizable, computable, and formally represented molecular genetics information and health information, via electronic health record (EHR) interfaces, can play a critical role in achieving precision medicine. In this study, we used cystic fibrosis as an example to build an Ontology-based Knowledge Base prototype on Cystic Fibrobis (OntoKBCF) to supply such information via an EHR prototype. In addition, we elaborate on the construction and representation principles, approaches, applications, and representation challenges that we faced in the construction of OntoKBCF. The principles and approaches can be referenced and applied in constructing other ontology-based domain knowledge bases.
    METHODS: First, we defined the scope of OntoKBCF according to possible clinical information needs about cystic fibrosis on both a molecular level and a clinical phenotype level. We then selected the knowledge sources to be represented in OntoKBCF. We utilized top-to-bottom content analysis and bottom-up construction to build OntoKBCF. Protégé-OWL was used to construct OntoKBCF. The construction principles included (1) to use existing basic terms as much as possible; (2) to use intersection and combination in representations; (3) to represent as many different types of facts as possible; and (4) to provide 2-5 examples for each type. HermiT 1.3.8.413 within Protégé-5.1.0 was used to check the consistency of OntoKBCF.
    RESULTS: OntoKBCF was constructed successfully, with the inclusion of 408 classes, 35 properties, and 113 equivalent classes. OntoKBCF includes both atomic concepts (such as amino acid) and complex concepts (such as \"adolescent female cystic fibrosis patient\") and their descriptions. We demonstrated that OntoKBCF could make customizable molecular and health information available automatically and usable via an EHR prototype. The main challenges include the provision of a more comprehensive account of different patient groups as well as the representation of uncertain knowledge, ambiguous concepts, and negative statements and more complicated and detailed molecular mechanisms or pathway information about cystic fibrosis.
    CONCLUSIONS: Although cystic fibrosis is just one example, based on the current structure of OntoKBCF, it should be relatively straightforward to extend the prototype to cover different topics. Moreover, the principles underpinning its development could be reused for building alternative human monogenetic diseases knowledge bases.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号