ANGELMAN SYNDROME NATURAL HISTORY STUDY

天使综合症自然史研究

• 批准号: 8356672
• 负责人: Carlos A. Bacino
• 金额: $ 1.54万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356672
• 关键词: Address; Adult; Angelman Syndrome; Autistic Disorder; Behavioral; Boston; Chromosomes; Clinical; Clinical Research; Clinical Trials; Communities; Data; Defect; Development; Developmental Delay Disorders; Diagnosis; Disease; Disease Progression; Economics; Evaluation; Family member; Funding; Future; Gait Ataxia; Genes; Genetic; Genotype; Grant; Individual; Intervention; Investigation; Knowledge; Laboratories; Life; Ligase Gene; Longevity; Maps; Medical; Medicine; Modality; Molecular; Molecular Abnormality; Molecular Diagnosis; Morbidity - disease rate; National Center for Research Resources; Natural History; Neonatal; Outcome; Participant; Patients; Pediatric Hospitals; Phase; Phenotype; Physicians; Principal Investigator; Qualifying; Quality-of-Life Assessment; Rare Diseases; Records; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Resources; Seizures; Sleep disturbances; Social Impacts; Source; Speech; Texas; Ubiquitin-Protein Ligase Complexes; United States National Institutes of Health; Visit; clinical Diagnosis; cohort; college; cost; design; experience; follow-up; mortality; multidisciplinary; prevent; psychologic; ubiquitin-protein ligase

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT Angelman syndrom (AS) is a nuerological disorder that causes global developmental delay, minimal or absent speech, seizures, uncoordinated gait (ataxia), sleep disturbances, and other medical and behavioral difficulties. AS is caused by deficiency of the maternally-transmitted gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. Although some aspects of AS are well known to the medical community, the natural history of AS has not been systematically described. Since AS is a rare disorder, few physicians follow more than a handful of patients at any given Center. A collaborative effort is needed to better understand the natural history of this rare condition. It is only with this knowledge that we will be able to formulate treatment interventions, devise therapies and propose future clinical trials. This study is part of an initiative under the auspices of the Rare Disease Clinical Research Netrowk and the NIH. This study is designed to conduct longitudinal multidisciplinary investigations on the natural history, morbidity and mortality of Angelman Syndrome (AS). We will collect detailed longitudinal data on a cohort of AS individuals to gain a better understanding of the disease progression, and follow the natural history of the clinical features of this patient cohort including assessment of quality of life and longevity. The participants to be recruited for the study will include 1) patients whohave a documented molecular diagnosis of AS and 2) patients with clear clinical diagnosis of Angelman Syndrome as determined by the Principal Investigator (PI) and the Co-investigators in this study but who don't have a known molecular defect. All participants will be seen every 12 months for 5 years during the first phase of accrual and follow-up, at Texas Children's Hospital (Baylor College of Medicine), and also at other centers that form part of this research endeavor including Children's Hospital of San Diego, Boston Children's Hospital, and the Greenwood Genetics Center. A second phase of 5 additional years of follow-up is also proposed. Clinical and relevant historical data will be collected during the clinical visit and examination and also by reviewing medical and laboratory records. Comparisons will be made within the clinically different groups of patients, as well as among the different molecular classes of AS individuals. HYPOTHESIS Conducting longitudinal multidisciplinary investigations in Angelman Syndrome (AS) drives the main hypothesis of this study . We propose to collect detailed longitudinal data on a cohort of AS individuals to gain a better understanding of the disease progression, and follow the natural history of the clinical features of this patient cohort icluding assessment of qualify of life and longevity. These systematic evaluations will allow us to gather valuable information that we can later apply to the follow-up and treatment modalities. We plan to look carefully at the different subtypes within this condition in order to formulate appropriate interventions. SPECIFIC AIMS The following specific aims address several key questions on AS: 1. Gain a better understanding of the natural history of this concition and its molecular sybtypes from the neonatal period to adulthood. 2. Understand the frequent complications experienced by patients with AS during their lifetime and identify possible co-morbid associations that can be prevented or ameliorated with medical intervention. 3. Establish a genotype-phenotype correlation over a broad spectrum of AS participatns (with regards to their molecular type). 4. Determine the mortality and morbidity in AS. 5. Determine if the molecular type of AS correlates with the co-morbid diagnosis of autism or other behavioral abnormalities. 6. Determine if AS is associated with a particular medical, psychological or genetic abnormality in the family members. 7. Determine the impact of Social and Economic level on the developmental outcome of patients with AS.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 摘要 Angelman综合征(AS)是一种神经系统疾病，导致全球发育迟缓、极少或缺少语言、癫痫发作、步态不协调(共济失调)、睡眠障碍以及其他医疗和行为困难。AS是由于定位于染色体15q11-q13的编码E6-AP泛素蛋白连接酶(基因符号UBE3A)的母系传播基因缺失所致。 尽管AS的某些方面已为医学界所熟知，但AS的自然历史尚未被系统地描述。由于AS是一种罕见的疾病，很少有医生在任何给定的中心跟踪超过少数患者。需要合作努力才能更好地了解这种罕见疾病的自然历史。只有有了这些知识，我们才能制定治疗干预措施，设计治疗方法，并提出未来的临床试验。这项研究是由罕见疾病临床研究网络和美国国立卫生研究院发起的一项倡议的一部分。 本研究旨在对安杰曼综合征(AS)的自然病史、发病率和死亡率进行纵向多学科调查。我们将收集一组AS个体的详细纵向数据，以更好地了解疾病的进展，并跟踪该患者队列的临床特征的自然历史，包括对生活质量和寿命的评估。 这项研究招募的参与者将包括1)有记载的AS分子诊断的患者和2)经首席调查员(PI)和本研究的联合调查员确定明确的临床诊断为Angelman综合征但没有已知分子缺陷的患者。 在评估和随访的第一阶段，所有参与者将在为期5年的第一阶段每12个月在德克萨斯儿童医院(贝勒医学院)以及圣地亚哥儿童医院、波士顿儿童医院和格林伍德遗传学中心等其他研究中心见到所有参与者。还提议在第二阶段再延长5年的后续行动。临床和相关历史数据将在临床访问和检查期间收集，也将通过审查医疗和实验室记录来收集。将在临床上不同的患者组中以及不同分子类别的AS个体之间进行比较。 假设 对Angelman综合征(AS)进行纵向多学科研究是本研究的主要假设。我们建议收集关于AS个体的详细纵向数据，以更好地了解疾病的进展，并跟踪该患者队列的临床特征的自然病史，包括对生活质量和寿命的评估。这些系统的评估将使我们能够收集有价值的信息，我们以后可以将这些信息应用于后续行动和治疗方式。我们计划仔细研究这种情况下的不同亚型，以便制定适当的干预措施。 具体目标 以下具体目标涉及AS的几个关键问题： 1.更好地了解这种疾病的自然历史及其从新生儿期到成年期的分子表型。 2.了解强直性脊柱炎患者在其一生中经常经历的并发症，并确定可以通过医疗干预预防或改善的可能的共病联系。 3.在广泛的AS参与者范围内(就其分子类型而言)建立基因-表型相关性。 4.测定AS的病死率和发病率。 5.确定AS的分子类型是否与自闭症或其他行为异常的共病诊断相关。 6.确定强直性脊柱炎是否与家庭成员的特定医学、心理或基因异常有关。 7.确定社会经济水平对强直性脊柱炎患者发育结局的影响。