S945L变异致囊性纤维化1例并文献复习

Cystic fibrosis caused by S945L variation：a case report and literature review

摘要:

目的：报道S945L变异致囊性纤维化（cystic fibrosis，CF）1例，并结合文献对该病在国内分子靶向治疗的现状及前景进行探讨。方法：对重庆医科大学附属儿童医院诊治的1例囊性纤维化跨膜传导调节因子（cystic fibrosis transmembrane conduc－tance regulator，CFTR）特定位点S945L变异的CF患儿临床资料及基因结果进行分析。以“囊性纤维化”及“cystic fibrosis”和“China”为关键词，对中国知网、万方、维普数据库及PubMed、Embase数据库建库至2019年7月收录的论文进行检索，总结中国报道的可以通过分子靶向治疗的特定CFTR变异的CF患儿临床资料及基因变异特点，并结合文献进行分析。结果：患儿平素反复呼吸道感染，营养状况差，胸部CT提示广泛支气管扩张，2次汗液氯离子浓度检测分别为74 mmol/L、75 mmol/L，基因检测结果：CFTR基因R851X/S945L复合杂合变异，最终确诊为CF。文献检索发现中国目前报道的通过基因确诊的90例CF患者中，共5例患者携带可以通过分子靶向治疗的特定变异位点。携带出现频率最高的G970D位点的15例患儿极有可能通过靶向治疗，但尚无临床研究证实。结论：临床上表现为反复呼吸道感染、生长发育落后，有广泛支气管扩张的患儿需警惕CF，需完善CFTR基因检测。中国CF患者中，可能符合靶向药物治疗条件的患儿所占比例大，治疗前景可观，条件允许情况下，需开展更多的临床研究，以期为这些患者延长寿命，提高生存质量。

Abstract:

Objective：To report one case of cystic fibrosis（CF） caused by S945L variation，and to investigate the present state and perspectives of molecular targeted therapy for this disease in China. Methods：The clinical data and gene mutation of a CF case caused by S945L mutation in cystic fibrosis transmembrane conductance regulator（CFTR） special site in Children’s Hospital of Chongqing Medical University were analyzed. The literature till July 2019 was searched with key words of “cystic fibrosis” and “China” in the database of CNKI，Wanfang，VIP，PubMed and Embase. The clinical data and gene mutation of patients with cystic fibrosis caused by special mutations of CFTR gene reported in China were summarized and analyzed in combination with the literature. Results：The patient had recurrent respiratory tract infection and poor nutritional status，with chest CT suggesting extensive bronchiectasis. Results of sweat chloride concentration test were 74 mmol/L and 75 mmol/L，respectively. Gene detection demonstrated CFTR gene R851X/S945L compound heterozygous mutation，which ws finally diagnosed as CF. According to the literature review，90 patients with CF were reported in China，and 5 patients carried specific mutation sites that could be treated with molecularly targeted treatment. The 15 children with the G970D mutation were most likely to be treated with gene targeting therapy，without confirmed clinical study. Conclusion：Children with recurrent respiratory tract infection，slow growth development and extensive bronchiectasis should guard against CF and the CFTR is in need. In China，more CF patients meet the requirements of targeted drug ther－apy，with considerable treatment prospect. Therefore，more clin－ical studies should be carried out when necessary，so as to in－crease patients’ life span and improve life quality.