中国人囊性纤维化及CFTR基因相关弥漫性支气管扩张的表型谱和突变谱鉴定

Cystic fibrosis (CF), a genetic disorder due to cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation, is the most common autosomal recessive disease in Caucasians, as well as a well-established cause of disseminated bronchiectasis (DB), a rapidly progressive and debilitating pulmonary illness. Patients usually suffer from recurrent respiratory infections requiring high dose of antibiotics, which, among others, results in a dramatic occurrence of drug-resistant strains of pathogens. CF has rarely been reported in Chinese patients, and there has been few, if any, research in this area. Our preliminary study on 6 Chinese CF patients seems to indicate that their CFTR gene mutations are different from mutations commonly detected in Caucasian population, and some of our patients' mutations have only been reported among Asians. Clinical manifestations of our CF patients also differ from classic CF, with fewer and less severe pancreatic involvement. We postulate that these atypical phenotypes might be the result of the unusual gene mutations. This study aims to further characterize the genotype and phenotype of Chinese CF patients, in the hope of devising practical diagnostic criteria for Chinese population on CF and CFTR-DB. In first stage, any clinically suspicious patient shall undergo a sweat test, and those with an abnormal result will be tested for CFTR gene mutation by direct DNA sequencing. Their clinical features and gene mutations shall be documented and analyzed, and a tentative diagnostic criterion will be formulated upon the result. In second stage, we shall screen for those commonly found CFTR mutations in Chinese population in 50 patients who fit our diagnostic criteria, thus to prove its validity and make adjustments. We hope by using our criterion, CF patients in China can be timely diagnosed and properly managed, and their quality of life improved as much as possible.

囊性纤维化（cystic fibrosis, CF）是白种人最常见的常染色体隐性遗传病，由CFTR基因突变引起；也是呼吸系统的常见病，弥漫性支气管扩张（disseminated bronchiectasis, DB）的病因之一。DB的肺功能恶化快，严重危害人类健康。目前中国没有DB相关的病因学和发病机制的研究。CF在中国人群极少报道。我们前期对6例CF患者的研究表明，中国人CF的表现不典型，常无胰腺功能异常，CFTR基因突变与欧美不同，均为少见突变，部分突变仅见于亚洲人群。 本研究拟收集可疑CF病例进行汗液氯离子测定，异常者50例经直接测序进行突变筛查，总结其突变谱和表型谱，提出中国人CF的临床及基因诊断标准。在此指导下，收集后续100例患者，进行突变高发位点的筛查，验证并完善此标准，建立中国人特有的CF及CFTR-DB的快速诊断程序，为患者提出合理而有效的个体化治疗方案，提高患者的疗效。

囊性纤维化（cystic fibrosis, CF）是白种人最常见的常染色体隐性遗传病，由CFTR基因突变引起；也是呼吸系统的常见病，弥漫性支气管扩张（disseminated bronchiectasis, DB）的病因之一。DB的肺功能恶化快，严重危害人类健康。目前中国没有DB相关的病因学和发病机制的研究。CF在中国人群极少报道。我们前期对5例CF患者的研究表明，中国人CF的表现不典型，常无胰腺功能异常，CFTR基因突变与欧美不同，均为少见突变，部分突变仅见于亚洲人群。.本研究收集了可疑CF病例进行汗液氯离子测定，共计确诊CF患者家系26个，CFTR-DB患者18例，经直接测序进行突变筛查，总结其突变谱和表型谱，进一步证实了中国人CF不但临床表现不典型，而且基因谱与欧美差异很大，不适宜采用欧美商业用途筛查平台进行检测，需要进行直接测序。中国人最常见的突变谱为G970D，占全部中国CF患者的12.1% (15/124)。且这些突变一旦合并有无义突变或是delta 508等严重突变，患者的临床表型常常较重。这些发现将为中国CF患者提供精准治疗的机会。