ABCA3 mutations associated with pediatric interstitial lung disease
ABCA3 mutations associated with pediatric interstitial lung disease
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DOI：
10.1164/rccm.200503-504oc
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发表时间：
2005-10-15
影响因子：
24.7
通讯作者：
Nogee, LM
中科院分区：
文献类型：
--
作者：
Bullard, JE;Wert, SE;Nogee, LM
原理：ABCA3是atp结合盒蛋白家族的一员，可介导多种底物（包括脂质）跨细胞膜的易位。编码ABCA3基因的突变最近在具有致命性表面活性剂缺乏症的足月新生儿中被发现。目的：验证ABCA3突变并不总是与致命性新生儿肺病相关，而是儿童间质性肺病的一个原因的假设。方法：对195例病因不明的慢性肺部疾病患儿进行DNA采集。研究人员对4名无亲和关系的脱屑性间质性肺炎患儿的ABCA3基因的30个编码外显子进行了测序，这些患儿在入组时年龄大于10岁，且诊断为脱屑性间质性肺炎。结果：4例脱屑性间质性肺炎患者（年龄分别为16岁、23岁和11岁）中有3例在两个等位基因上都发现了ABCA3突变。这三个人都有相同的错义突变（E292v）和第二个独特的突变。在没有肺部疾病的成年人的200个对照等位基因上没有发现E292V突变，但在其余研究患者中，另外7名患者在一个等位基因上发现了E292V突变。对3例患者表面活性剂蛋白表达的免疫组织化学分析显示表面活性剂蛋白- b的特异性染色模式，这与几例因ABCA3突变而致死性肺病的婴儿观察到的模式相同。结论：ABCA3突变可引起某些类型的儿科间质性肺疾病。
Rationale: ABCA3 is a member of the ATP-binding cassette family of proteins that mediate the translocation of a wide variety of substrates, including lipids, across cellular membranes. Mutations in the gene encoding ABCA3 were recently identified in full-term neonates with fatal surfactant deficiency.Objective: To test the hypothesis that ABCA3 mutations are not always associated with fatal neonatal lung disease but are a cause of pediatric interstitial lung disease.Methods: DNA samples were obtained from 195 children with chronic lung disease of unknown etiology. The 30 coding exons of the ABCA3 gene were sequenced in four unrelated children with a referring diagnosis of desquamative interstitial pneumonitis and who were older than 10 years at the time of enrollment.Results: Three of four patients (ages 16, 23, and 11 years) with desquamative interstitial pneumonitis had ABCA3 mutations identified on both alleles. All three had the same missense mutation (E292v) and a second unique mutation. The E292V mutation was not found on 200 control alleles from adults without lung disease, but seven additional patients of the remaining study patients had the E292V mutation on one allele. Immunohistochemical analysis of surfactant protein expression in three patients revealed a specific staining pattern for surfactant protein-B, which was the same pattern observed in several infants with fatal lung disease due to ABCA3 mutations.Conclusion: ABCA3 mutations cause some types of interstitial lung disease in pediatric patients.