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; 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 抽象的 Angelman综合症（AS）是一种刺激性疾病，会导致全球发育迟缓，最小或缺乏言语，癫痫发作，不协调步态（共济失调），睡眠障碍以及其他医学和行为困难。 这是由编码E6-AP泛素 - 蛋白连接酶（基因符号UBE3A）映射到染色体15q11-Q13染色体的母体转移基因的缺乏。 尽管医学界的某些方面是AS的某些方面，但尚未系统地描述AS的自然历史。 由于罕见疾病也是如此，很少有医生在任何给定的中心都遵循少数患者。 需要进行协作努力，以更好地了解这种罕见情况的自然历史。 只有知识，我们才能够制定治疗干预措施，设计疗法并提出未来的临床试验。 这项研究是罕见疾病临床研究Netrowk和NIH的主持下的一项倡议的一部分。 这项研究旨在对Angelman综合征的自然历史，发病率和死亡率（AS）进行纵向多学科研究。 我们将收集有关AS个人队列的详细纵向数据，以更好地了解疾病进展，并遵循该患者队列的临床特征的自然历史，包括评估生活质量和寿命。 该研究的招募的参与者将包括1）患者，该患者已被证明是AS和2）在本研究中首席研究员（PI）确定的Angelman综合征明确临床诊断的患者和尚无已知分子缺陷的患者。 在得克萨斯州儿童医院（贝勒医学院）的第一阶段和随访的第一阶段，将每12个月观察所有参与者，持续5年，以及在包括圣地亚哥儿童医院，波士顿儿童医院和格林伍德遗传学中心，包括这项研究努力的其他中心。 还提出了另外5年的随访的第二阶段。 临床和相关的历史数据将在临床访问和检查期间收集，并通过审查医疗和实验室记录。 比较将在临床上不同的患者组以及个体的不同分子类中进行比较。 假设 在Angelman综合征（AS）进行纵向多学科研究（AS）推动了这项研究的主要假设。 我们建议收集有关一个人群的详细纵向数据，以更好地了解疾病的进展，并遵循该患者队列的临床特征的自然历史，以评估有资格对寿命和寿命的评估。 这些系统的评估将使我们能够收集有价值的信息，以后我们可以将其应用于后续方法和治疗方式。 我们计划在这种情况下仔细查看不同的子类型，以制定适当的干预措施。 具体目标 以下特定目的解决了以下几个关键问题： 1。从新生儿时期到成年后，可以更好地了解这一法案的自然历史及其分子型。 2。了解患者在其一生中经历的频繁并发症，并确定可以通过医疗干预来预防或改善的可能的合并关联。 3。建立在参与者的广泛范围（关于它们的分子类型）上的基因型 - 表型相关性。 4。确定AS的死亡率和发病率。 5。确定AS的分子类型是否与自闭症或其他行为异常的合并诊断相关。 6.确定家庭成员中特定的医学，心理或遗传异常是否相关。 7.确定社会和经济水平对AS患者的发展结果的影响。