13th International Workshop on Ataxia-Telangiectasia and ATM

描述（由申请方提供）：共济失调-毛细血管扩张症（A-T）是一种罕见的常染色体隐性遗传疾病，全球每40，000例活产婴儿中约有1例受影响。其特征在于进行性小脑共济失调、毛细血管扩张、免疫缺陷、基因组不稳定性、辐射敏感性和癌症（通常为淋巴瘤或白血病）的发病率显著增加。A-T的症状通常在生命的最初几年表现为步态不稳。神经肌肉控制的丧失是无情的，到了十几岁，孩子们通常只能坐在轮椅上。他们还存在神经性吞咽问题，这可能导致吸入性肺炎和窦肺感染。据估计，高达1%的普通人群携带ATM（共济失调-毛细血管扩张突变）基因的一个等位基因突变，ATM杂合子患乳腺癌的风险增加。ATM基因编码一个大的（369 kDa）蛋白，ATM，它是磷脂酰肌醇3激酶家族的丝氨酸/苏氨酸蛋白激酶的成员。ATM的主要作用似乎是在DNA损伤识别，特别是双链DNA断裂。缺乏ATM的细胞对电离辐射（IR）高度敏感，并且在响应IR和其他DNA损伤剂的多个细胞周期检查点的激活中存在缺陷。理解ATM的功能对于理解ATM在神经发育和神经变性中的作用、A-T患者和ATM杂合子中癌症易感性增加的分子基础以及控制细胞如何对辐射损伤和拟放射性化疗药物作出反应的分子机制具有相当重要的意义。A-T也已成为研究治疗遗传疾病的突变靶向药物的模型，因为有数百种患者来源的细胞系可供使用，并具有已鉴定的突变。第13届共济失调-毛细血管扩张症和ATM国际研讨会的目的：会议的目的是汇集一组国际基础和临床研究人员，他们致力于A-T和相关神经退行性疾病的各个方面，以及ATM在癌症中的作用，DNA损伤反应和病毒感染。我们的目标是促进研究，从而更好地理解和治疗A-T。会议的具体重点领域将包括ATM和相关蛋白在DNA损伤反应中的作用，染色质和基因组不稳定性在ATM激活中的重要性，ATM在发育中的神经系统和神经变性中的作用，A-T的动物模型，乳腺癌和其他人类癌症中的ATM突变，ATM突变的流行病学，以及A-T新疗法的开发和全球A-T患者未来临床试验的设计。我们还希望鼓励新的年轻研究人员进行临床和基础A-T/ATM研究。 公共卫生相关性：会议的具体重点领域将包括ATM和相关蛋白在DNA损伤反应中的作用，染色质和基因组不稳定性在ATM激活中的重要性，ATM在发育中的神经系统和神经变性中的作用，A-T的动物模型，乳腺癌和其他人类癌症中的ATM突变，ATM突变的流行病学，以及A-T新疗法的开发和全球A-T患者未来临床试验的设计。我们还希望鼓励新的年轻研究人员进行临床和基础A-T/ATM研究。

DESCRIPTION (provided by applicant): Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder that affects approximately 1 in 40,000 live births worldwide. It is characterized by a progressive cerebellar ataxia, telangiectasia, immunodeficiency, genomic instability, radiation sensitivity, and a markedly increased incidence of cancer, usually lymphoma or leukemia. Symptoms of A-T are typically manifested during the first few years of life with a wobbly gait. Loss of neuromuscular control is relentless and, by their teens, the children are usually confined to a wheel chair. They also have neurological swallowing problems which can lead to aspiration pneumonia and sinupulmonary infections. It has been estimated that up to 1% of the general population carries mutations in one allele of the ATM (ataxia-telangiectasia mutated) gene and ATM heterozygotes have an increased risk of developing breast cancer. The ATM gene encodes a large (369 kDa) protein, ATM, which is a member of the phosphatidyl inositol 3 kinase family of serine/threonine protein kinases. The major role of ATM appears to be in DNA damage recognition, especially of double strand DNA breaks. Cells that lack ATM are highly sensitive to ionizing radiation (IR) and are defective in the activation of multiple cell cycle checkpoints in response to IR and other DNA damaging agents. Understanding the function of ATM is of considerable importance to understanding the role of ATM in neural development and neurodegeneration, the molecular basis for increased cancer predisposition in A-T patients and ATM heterozygotes, and the molecular mechanisms that control how cells respond to radiation damage and radiomimetic chemotherapeutic drugs. A-T has also become a model for the study of mutation-targeted drugs for treating genetic diseases since hundreds of patient-derived cell lines are available, with identified mutations. Objectives of the 13th International Workshop on Ataxia-Telangiectasia and ATM meeting: The objectives of the meeting are to bring together an international group of basic and clinical researchers working on various aspects of A-T and related neurodegenerative diseases, as well as on the role of ATM in cancer, the DNA damage response, and in viral infections. Our goal is to stimulate research that will lead to better understanding and treatment of A-T. Specific areas of focus of the meeting will include the role of ATM and related proteins in the DNA damage response, the importance of chromatin and genomic instability in the activation of ATM, the role of ATM in the developing nervous system and in neurodegeneration, animal models of A-T, ATM mutations in breast and other human cancers, the epidemiology of ATM mutations, and the development of new treatments for A-T and the design of future clinical trials for A-T patients worldwide. We also hope to encourage new young investigators to both clinical and basic A-T/ATM research. PUBLIC HEALTH RELEVANCE: Specific areas of focus of the meeting will include the role of ATM and related proteins in the DNA damage response, the importance of chromatin and genomic instability in the activation of ATM, the role of ATM in the developing nervous system and in neurodegeneration, animal models of A-T, ATM mutations in breast and other human cancers, the epidemiology of ATM mutations, and the development of new treatments for A-T and the design of future clinical trials for A-T patients worldwide. We also hope to encourage new young investigators to both clinical and basic A-T/ATM research.