ASSOCIATION OF CFTR MUTATIONS AND BORDERLINE SWEAT TESTS

Cf是一种遗传性疾病，发生在1/2000出生时。基因 本病致囊性跨膜性纤维化 调节蛋白(CFTR)。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 器官受累和CF严重程度的变异性。一种氯化物汗 值大于70mEq/L一直是诊断的金标准 参见“临界值”(40-70 mEq/L)通常与轻度CF有关 症状，但与CF诊断无关。许多患者患有轻度的 与在这一边缘人群中观察到的肺表型相似 是从未做过汗液测试的成年人。基于 假设一个轻微的、胰腺充足的、慢性梗阻 伴有“交界性”汗液氯化物的肺部疾病表型与 Cftr基因突变(S)，申请人将描述 1)大量边缘人群的表型和2)患有 几项明确的纵向研究中的慢性呼吸系统疾病 人口。然后，将在这些文件中确定CFTR型 通过ASO、SSCP和DNA测序，并基于初步数据 这表明在这些人群中存在独特的CFTR型， 开发一个适当突变的分子遗传筛查小组。这个 慢性衰弱性肺疾病与其他疾病关联的意义 慢性支气管炎和慢性阻塞性肺 疾病)中携带CFTR基因异常将有助于对 这些疾病的病理生理学和潜在的治疗方法。

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.