一种新的ABCA3基因复合杂合突变导致儿童弥漫性肺间质病一例

A novel compound heterozygous mutation in ABCA3 gene in a child with diffuse parenchymal lung disease

目的 总结一种新的ABCA3基因复合杂合突变导致的儿童弥漫性肺间质病的临床特点并探讨突变基因型与表型之间的关系.方法 回顾性分析2016年12月深圳市儿童医院呼吸科确诊的1例由ABCA3基因复合杂合突变导致儿童弥漫性肺间质病患儿的临床资料,以＂ABCA3基因＂或＂ABCA3 gene＂为关键词搜索了2017年4月之前更新的万方中文数据库、Pubmed及千人基因组数据库（1000Genomes）、人类基因突变数据库（HGMD）、EXAC基因数据库,总结ABCA3基因突变患儿的临床表型与基因型的关系.结果 患儿女,1岁9月龄,1岁3月龄起病,以＂慢性咳嗽、气促、发绀、生长发育落后＂为主要表现,常规治疗后症状进行性加重,体格检查示营养不良、呼吸困难及杵状指.肺部高分辨CT提示双肺弥漫性磨玻璃影,小叶间隔增厚,胸膜下多发小叶间隔旁气肿.采用二代测序方法证实患儿存在ABCA3基因复合杂合突变（c.1755delC＋c.2890G〉A）,并且分别来源于父母亲,搜索文献及数据库无该复合杂合突变的报道.结论 c.1755delC＋c.2890G〉A是一种新的ABCA3基因复合杂合突变,可导致儿童弥漫性肺间质病,其临床表型与基因型相关.

Objective To summarize the clinical characteristics of the diffuse parenchymal lung diseases in a child caused by a novel compound heterozygous ABCA3 mutation and explore the association between the phenotype and ABCA3 mutation. Method The clinical material of a patient diagnosed with diffuse parenchymal lung disease with ABCA3 mutation in December 2016 in Shenzhen Children＇＇s Hospital was analyzed. The information about ABCA3 gene mutation updated before April, 2017 was searched and collected from the gene databases （including 1000Genomes,HGMD,EXAC） and the literatures （including Wanfang Chinese database and Pubmed）. Result The girl was one year and nine months old. She presented with chronic cough, tachypnea, cyanosis and failure to thrive since she was one year and three months old. Her condition gradually deteriorated after she was empirically treated. Physical examination showed malnutrition, tachypnea and clubbed-fingers. Her high resolution computed tomography （HRCT） revealed diffused ground-glass opacities, thickened interlobular septum, and multiple subpleural small air-filled lung cysts. The second generation sequencing study identified a novel compound heterozygous mutation（c.1755delC＋c.2890G〉A）in her ABCA3 gene, which derived respectively from her parents and has not been reported in the database and the literatures mentioned above. Conclusion c.1755delC＋c.2890G〉A is a new kind of compound heterozygous mutation in ABCA3, which can cause children＇＇s diffuse parenchymal lung disease. Its phenotype is related to its genotype.