1st International SYNGAP1 Conference

项目摘要 本提案的目标是确保资金支持第一届国际SYNGAP1会议。MRD5 (MIM#：612621; www.omim.org/entry/612621）是最近发现的一种零星形式的智力残疾 （ID）。这种疾病是由SYNGAP 1基因中的有害的从头突变引起的，该基因编码 突触RasGAP，SynGAP。MRD 5的症状包括认知障碍和严重受损 表达性和接受性语言。癫痫、ASD和ADHD是常见的共病， 在这些患者中，SYNGAP 1中的致病性突变令人惊讶地常见， 据报道，1 - 4/10，000的个体，或约1 - 2%的所有ID病例，使其成为最常见的病例之一 在SYNGAP 1的情况下，召开一次国际会议， 所有相关利益相关者（即患者家属、临床医生和研究人员），因为对 这种新出现的大脑紊乱虽然已知SynGAP蛋白对于调节学习和神经功能至关重要， 尽管SynGAP蛋白在人类和小鼠中的兴奋性，但仍不清楚功能性SynGAP蛋白的丧失如何导致 疾病的症状。此外，人们普遍缺乏对这一疾病的认识，导致延误 没有集中的位置来访问医疗、研究或患者信息。最后， 患者家属很难获得尖端的医疗和科学专业知识，这些知识将使他们的 对疾病的理解。因此，我们认为，迫切需要举行这次会议。的 拟议的会议将汇集利益攸关方，其主要目标是最大限度地提高科学 通过建立高效和协同的协作方法， 确定有效的治疗方法。我们有来自领先的临床医生和研究人员的承诺， 研究SynGAP生物学和相关的人类疾病。重要的是，会议将结合 与主要的MRD 5患者支持网络Bridge-the GAP（www.example.com）合作， 几个有受影响儿童的家庭的出席。专题讨论会将包括与监测和报告发展5有关的会议 临床遗传学/患者表型，Syngap 1神经生物学，神经发育中的常见底物 疾病，癫痫遗传学，RASopathies的翻译方法，以及罕见疾病的加速翻译 遗传性疾病。我们预计将为初级调查人员创造有影响力的机会，包括 妇女和少数民族，参加科学交流，并会见MRD 5患者及其家属。关键 预计这次会议的成果包括：（一）建立网络和建立合作研究， 临床推广计划;（ii）产生关于MRD 5发病机制和可能治疗的新想法; (iii)扩大MRD 5研究和临床社区;以及（iv）建立国际MRD 5 研究和临床网络，以促进充分合作，多实验室基础研究，并鼓励 启动患者登记和自然史研究，以推进患者护理和治疗。

Project Summary The goal of this proposal is to secure funds to support the 1st International SYNGAP1 Conference. MRD5 (MIM#: 612621; www.omim.org/entry/612621) is a recently discovered sporadic form of intellectual disability (ID). This disorder is caused by deleterious de novo mutations in the SYNGAP1 gene, which encodes the synaptic RasGAP, SynGAP. Symptoms of MRD5 include cognitive impairment and severely impaired expressive and receptive language. Epilepsy, ASD and ADHD are common comorbid conditions often described in these patients. Pathogenic mutations in SYNGAP1 are surprisingly common, with the incidence reported as 1-4/10,000 individuals, or approximately 1-2% of all ID cases, making it one of the most common genetic causes of ID. It is crucial in the case of SYNGAP1 to have an international meeting bringing together all relevant stakeholders (i.e. patient families, clinicians and researchers) because so little is understood about this emerging brain disorder. While it is known that SynGAP protein is critical for regulating learning and neural excitability in both humans and mice, it remains unclear how loss of functional SynGAP protein leads to symptoms of the disorder. Furthermore, there is a general lack of awareness of the disease, resulting in delay of diagnosis and there is no centralized location to access medical, research, or patient information. Lastly, patient families have poor access to cutting-edge medical and scientific expertise that will inform their understanding of the disorder. Therefore, we believe that there is an urgent need to hold this meeting. The proposed conference will bring together stakeholders with the primary goal of maximizing scientific resources by building collaborative approaches that are efficient and synergistic, thereby accelerating the identification of effective treatments. We have commitments from the leading clinicians and researchers studying SynGAP biology and the related human disorders. Importantly, the meeting will be run in conjunction with the major MRD5 patient support network, Bridge-the GAP (www.bridgesyngap.org), which will organize the attendance of several families with affected children. The symposium will include sessions related to MRD5 clinical genetics/patient phenotypes, Syngap1 neurobiology, common substrates in neurodevelopmental disorders, epilepsy genetics, translational approaches in RASopathies, and accelerating translation in rare genetic disorders. We anticipate the creation of impactful opportunities for junior investigators, including women and minorities, to participate in scientific exchange and to meet MRD5 patients and their families. Key outcomes expected from this meeting include: (i) networking and establishment of collaborative research and clinical outreach programs; (ii) generation of new ideas on the pathogenesis and possible treatment of MRD5; (iii) expansion of the MRD5 research and clinical community; and (iv) establishment of an international MRD5 research and clinical network to foster fully collaborative, multi-laboratory basic research and to encourage initiation of a patient registry and natural history study in order to advance patient care and treatment.