ASSOCIATION OF CFTR MUTATIONS AND BORDERLINE SWEAT TESTS

CF是一种遗传性疾病，发生率为1/2000。基因 负责这种疾病产生囊性纤维化跨膜 调节因子（CFTR）蛋白。这种蛋白质被认为可以调节 氯离子通过细胞膜。CFTR基因的不同突变 可能会导致不同的表型，如 CF的器官受累和严重程度的变异性。一种汗液氯化物 值大于70 mEq/L一直是诊断的金标准， 参见“临界”（40-70 mEq/L）值通常与轻度CF相关 症状，但与CF诊断无关。许多患有轻度 肺表型与该临界人群中观察到的相似 是从未做过汗液测试的成年人。基于 假设一个轻微的，胰腺足够的，慢性阻塞性 具有“临界”汗液氯化物的肺部疾病表型与 CFTR基因中的突变，申请人将表征 表型1）大量的边缘人群和2）受试者 几项定义明确的纵向研究中的慢性呼吸系统疾病 人口。然后将在这些研究中表征CFTR基因型。 通过阿索，SSCP和DNA测序，并根据初步数据， 这表明在这些人群中存在独特的CFTR基因型， 开发一个分子遗传学筛查面板，以寻找合适的突变。的 将慢性衰弱性肺病与其他 慢性支气管炎、慢性阻塞性肺疾病 疾病）与CFTR基因异常将提高洞察力 这些疾病的病理生理学和潜在的治疗。

CF is an inherited disorder which occurs in 1/2000 births. The gene responsible for this disease produces the Cystic Fibrosis Transmembrane Regulator (CFTR) protein. This protein is thought to regulate passage of chloride ions through cell membranes. Different mutations in the CFTR gene may potentially lead to different phenotypes, as demonstrated by the variability in organ involvement and severity of CF. A sweat chloride value greater than 70 mEq/L has been the gold standard for diagnosis in CF. "Borderline" (40-70 mEq/L) values are often associated with mild CF symptoms but not tied to a CF diagnosis. Many patients with a mild pulmonary phenotype similar to that observed in this borderline population are adults who have never had sweat tests performed. Based on the hypotheses that a mild, pancreatic sufficient, chronic obstructive pulmonary disease phenotype with "borderline" sweat chloride is linked to mutation(s) in the CFTR gene, the applicant will characterize the phenotypes of 1) a large population of borderlines and 2) subjects with chronic respiratory disorders from several well defined longitudinal study populations. The CFTR genotypes will then be characterized in these populations by ASO, SSCP and DNA sequencing, and based on preliminary data that suggests unique CFTR genotypes are presented in these populations, develop a molecular genetic screening panel for appropriate mutations. The significance of associating chronic debilitating pulmonary disorders other than CF (such as chronic bronchitis and chronic obstructive pulmonary disease) with CFTR gene abnormalIties would improve insight into the pathophysiology and potential therapy of those disorders.