分子诊断儿童囊性纤维化二例并中国人囊性纤维化文献复习

Molecular diagnosis of two Chinese cystic fibrosis children and literature review

目的探讨中国人囊性纤维化的临床和分子学特点。方法对首都医科大学附属北京儿童医院2010年和2015年诊断的2例儿童囊性纤维化病例资料进行总结，并通过关键词“囊性纤维化、中国人”“cystic fibrosis，Chinese”分别检索中国知网（CNKI）、万方和PubMed数据库（1975—2015年）文献报道的中国囊性纤维化患者资料，分析总结其临床和分子学特点。结果例1女，10岁；例2男，8月龄；均有反复咳嗽、支气管扩张。例1伴有肝硬化和汗液氯离子增高，例2伴生长发育落后和脂肪泻。CFTR基因检查可见e．595C〉T、C．2290C〉T突变。符合检索条件21篇文献报道36例中国患者，年龄4月龄至28岁，其中男16例、女20例，加上本组2例，一共38例。所有患者均有反复呼吸道感染，71％（27／38）存在营养不良，39％（15／38）有慢性腹泻；另有42％（16／38）有其他消化系统表现，包括黄疸（4例）、肝脏增大（11例）、腹水（2例）、胰腺萎缩（3例）。5例有明确家族遗传病史，3例患者父母为近亲结婚。74％（28／38）的患者汗氯水平增高（52～327mmol／L）。有报道的16例中有8例存在胰腺功能不全，20例中有18例存在支气管扩张。13例（34％）患者死亡。25例患者进行CFTR基因检测，发现29个不同的突变位点，较为多见的突变为e．1766＋5G〉T（5例）、C．2083dupG和c．2684G〉A（3例）。结论中国人囊性纤维化主要以呼吸道症状为主，绝大多数患者存在支气管扩张症，部分患者存在营养不良和消化道症状，约半数存在胰腺功能不全，CFTR基因突变位点多样，均为少见突变。

Objective To investigate the clinical manifestations and molecular features of cystic fibrosis in Chinese children. Method A retrospective analysis of two pediatric cystic fibrosis cases diagnosed by gene test in Beijing Children＇s Hospital, Capital Medical University from 2010 to 2015, and Chinese cystic fibrosis reported patients searched of ＂ cystic fibrosis, Chinese＂ on Chinese databases （ CNKI, Wanfang Data） and PubMed from 1975 to 2015. The clinical manifestations and molecular features were analyzed. Result One of the two newly diagnosed cystic fibrosis cases was a 10-year old girl who suffered from reccurent cough with expectoration and associated with cirrhosis. Sweat tests showed increased chloride twice with the lower level of 306. 82 mmol/L. The other was an 8-month old boy with receurent pneumonia from neonate, failure to thrive and fatty diarrhea. Two children had various degrees of bronchiectasis and massive sticky secretion on the bronchoscopy. They had no family history and their parents had no consanguineous marriage, CFTR mutations of c. 595C 〉 T and c. 2290C 〉 T were found in gene tests. On the database, twenty-one reports involving thirty-six Chinese patients （16 males and 20 females） were retrieved. Together with this group of 2 cases, a total of 38 cases were involved. The age at diagnosis was 4 months to 28 years with a median age of 10 years. All patients had reccurent respiratory infections, twenty-seven cases （71%） had malnutrition, fifteen （39%） had chronic diarrhea, and 16 cases （42%） had other digestive manifestations, including jaundice （4 cases）, hepatomegaly （11 cases）, ascites （2 cases） and pancreatic atrophy （3 cases）. Five cases had a positive family history and six cases had a suspicious family history. Consanguineous marriage was found ill three families. Sweat test revealed elevated chloride （52-327 retool/l,）in 28 cases. Eight of the 16 patients who performed pancreatic exoerinc function examination showed pancreatic insufficiency. Eighteen of the 20 patients described lhe image manifestation of bronchieetasis, The age at death of 13 patients （34%） was 4 months to 25 years with a median of 11 years. Twenty-nine rare CFTR mutations were found in 25 tesled patients, and c. 1766 ＋5G 〉 T（5 cases）, c. 2083dupG and c. 2684G 〉 A （3 cases） held the top three mutation patterns. Conclusion Respirato/7 symptoms and brnnchiectasis are the main manit〉stalions of Chinese cystic fibrosis palients, although some of them may be associated with malnutrition, digestive symptoms and pancreatic insufficiency. CFTR mutations are various and rare in Caucasians.