CLINICAL CHARACTERIZATION OF FAMILIAL SPONTANEOUS PNEUMOTHORAX

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 据估计，大约10%的自发性气胸患者有家族病史。 近年来，很明显，在一些家庭中，气胸是一种已知的单基因疾病的表现，如α-1-抗胰蛋白酶缺乏症或马凡氏综合征。 在其他家庭中，没有已知的疾病可以解释气胸。我们认为家族性自发性气胸是一种不同于其他单基因疾病的疾病。为了验证这一假设，我们收集了一些患有这种疾病的家庭;受影响的个人没有任何实验室或临床特征的α-1-抗胰蛋白酶缺乏症，马凡综合征，或任何其他已知的疾病与自发性气胸。 在最大的家族中，我们排除了两个与自发性气胸相关的遗传位点。我们提出了一些测试受影响的个人和那些在发展的疾病，将提供详细的临床特征，这种疾病的风险。 首先，我们将进行详细的体格检查，特别注意肌肉骨骼、皮肤和肺部系统。鉴于自发性气胸与虚弱体质之间的已知关联，将进行身高、臂展、体重、坐高、上臂和大腿长度的人体测量，并与NHANES III标准进行比较。将测定α-1-抗胰蛋白酶定量测量值。肺功能检查包括肺量测定法、身体体积描记法和弥散能力，将测量生理呼吸力学。胸部的计算机断层扫描（CT）将被用来观察周围的胸膜下大泡或肺孔，这是这种疾病的标志。 这些提出的特征可以识别具有中间表型的个体，具有正常肺量测定和不能由显著吸烟史解释的局部肺气肿病变的放射学证据的相关家庭成员。建议详细的临床表征这种疾病将是必不可少的，以确定这种疾病的分子基础，在未来使用遗传学方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It has been estimated that approximately 10% of individuals who have a spontaneous pneumothorax have a positive family history of the disorder. In recent years it has become evident that in some families the pneumothorax is a manifestation of a known monogenic disease, such as alpha-1-antitrypsin deficiency or Marfan syndrome. In other families, no known disease can explain the pneumothoraces. We propose that familial spontaneous pneumothorax is a disease distinct from other monogenic disorders. To test this hypothesis, we have collected a number of families with this disorder; affected individuals who do not have any of the laboratory or clinical features of alpha-1-antitrypsin deficiency, Marfan syndrome, or any other known disorder associated with spontaneous pneumothoraces. In the largest family we have ruled out two genetic loci associated with spontaneous pneumothoraces. We propose a number of tests for affected individuals and those at-risk for developing the disease that will provide detailed clinical characterization of the features of this disease. First, we will perform detailed physical exams with special attention toward the musculoskeletal, dermatologic, and pulmonary systems. Given the known association between spontaneous pneumothorax and an asthenic body habitus, anthropometric measurements of height, arm span, weight, sitting height, upper arm and upper leg lengths will be taken and compared with NHANES III norms. Alpha-1-antitrypsin quantitative measurements will be determined. Pulmonary function tests including spirometry, body plethysmography, and diffusion capacity will measure physiologic respiratory mechanics. Computed tomography (CT) scans of the chest will be taken in an effort to visualize the peripheral, subpleural blebs or holes in the lung that are the hallmark of this disorder. These proposed characteristics may identify individuals who have an intermediate phenotype, related family members who have normal spirometry and radiographic evidence of localized emphysematous-lesions of the lung not explained by a significant smoking history. The proposed detailed clinical characterization of this disorder will be essential for determining the molecular basis of this disorder by using genetic methods in the future.