ABCA3杂合突变病例临床分析  

Clinical analysis of heterozygous ABCA3 mutations in children

作　　者：徐秀娟[1] 刘恩梅[1] 罗征秀[1] 罗健[1] 符州[1] 

机构地区：[1]重庆医科大学附属儿童医院呼吸一病房,400014

出　　处：《中华儿科杂志》2014年第4期244-247,共4页Chinese Journal of Pediatrics

基　　金：重庆市卫生局科技项目（2009-2-245） 重庆医科大学附属儿童医院的大力支持及临床罕见疑难病专项（hjyn2013-1）基金资助

摘　　要：目的 了解ATP结合盒A家族成分3（ABCA3）突变与新生儿呼吸窘迫综合征（NRDS）及儿童肺部疾病的相关性.方法 筛查2010年1月至2011年12月重庆医科大学附属儿童医院呼吸科和新生儿科住院的38例患呼吸系统疾病患儿（均为汉族）的ABCA3基因2个位点：c.875A＞T（p.E292V）、c.G3661A（p.G1221S）,分析突变病例的临床表现、影像学特点及基因检测结果.结果 共4例患儿发生基因突变,其中2例为c.875A＞T（p.E292V）杂合突变（例2女,3h;例4男,52 d）;2例为c.G3661A（p.G1221S）杂合突变（例1男,78 d;例3女,15岁1个月）;均否认呼吸系统疾病家族史.例1、2、4在生后患NRDS,例1、2为早产;例3生后正常,入院后临床诊断肺间质疾病（ILD）.4例患儿临床转归不同：例1有反复喘息,需吸入激素治疗,生长发育可;例2因脱机困难死亡;例3好转出院后失访;例4生长发育正常,未发现ABCA3突变位点与临床预后有明确的相关性.结论 ABCA3基因突变与多种婴幼儿肺疾病有关,包括NRDS到儿童ILD.早期识别ABCA3基因突变情况,及早诊断,有助于早期判断疾病预后、早期干预及开展遗传咨询提供依据.Objective To investigate the association of ATP-binding cassette transporter A3 （ABCA3） gene mutations with severe neonatal respiratory distress syndrome （NRDS） and lung disease in children.Method Thirty-eight children hospitalized with respiratory disorders in Children＇s Hospital of Chongqing Medical University from January 2010 to December 2011 were screened.Two mutations （E292V,G1221S） in the ABCA3 gene were identified.Interstitial lung disease （ILD） was present in 10 cases,NRDS was found in 23 and congenital pulmonary dysplasia in 5 cases.There were 24 males and 14 females,with an age range of 1 hour to 15 years.Genomic DNA was prepared from blood samples and sequences were analyzed by polymerase chain reaction （PCR）.Clinical feature,imaging characteristics and the results of gene detection were retrospectively analyzed.Result Four cases with ABCA3 gene mutations were found; 2 patients （case 2 and case 4） had the heterozygous mutation of ABCA3 E292V.One was a 3-hour-old girl and another was a 52-day-old boy,2 patients （case 1 and case 4） had the heterozygous mutation of ABCA3 G1221S.One was a 78-day-old boy and another was a girl,15 years and one month old.The family history was negative for respiratory disease.Three patients （case 1,2,4） had NRDS and 2 （case 1,2） of them were premature.One patient （case 3） had normal growth and development.She was diagnosed clinically as interstitial lung disease （ILD） after admission.The clinical outcomes of 4 cases were various.Case 1 had recurrent wheezing and inhaled corticosteroid was needed.Case 2 died because she failed to wean from mechanical ventilator.Case 3 was discharged with improvement but lost to follow-up.Case 4 grows normally.Conclusion Genetic variants within ABCA3 may be the genetic causes or background of a contributor to some unexplained refractory NRDS,and chronic lung disease developed in latter childhood.Identification of ABCA3 genetic variants in NRDS infants is important to offer genetic counseling,as we

关 键 词：ATP结合匣式转运子 突变 呼吸窘迫综合征 新生儿 肺疾病 间质性 

分 类 号：R725.6[医药卫生—儿科]