Saugstad Ola D, Hansen Thor Willy Ruud, Rønnestad Arild, Nakstad Britt, Tølløfsrud Per Arne, Reinholt Finn, Hamvas Aaron, Coles F Sessions, Dean Michael, Wert Susan E, Whitsett Jeffrey A, Nogee Lawrence M
Department of Pediatric Research, Rikshospitalet-Radiumhospitalet Health Trust, University of Oslo, Oslo, Norway.
Acta Paediatr. 2007 Feb;96(2):185-90. doi: 10.1111/j.1651-2227.2007.00016.x.
To investigate whether intractable respiratory distress syndrome in three Norwegian term infants was due to mutations in the ABCA3 gene.
The genes encoding SP-B (SFTPB), SP-C (SFTPC), and ABCA3 (ABCA3) were sequenced from the parents of one infant and two unrelated infants with fatal neonatal lung disease. Lung tissue was examined by histology, immunohistochemistry and electron microscopy.
Novel ABCA3 mutations were identified in each family. One patient had a phenotype differing from previous descriptions of this disease with an initial uneventful period. The diagnosis was established 19 years after death by analysing DNA material from the parents, with an ABCA3 mutation identified on one allele in each parent. The other two infants had more typical clinical courses with the onset of respiratory symptoms immediately after birth. ABCA3 mutations were identified on both alleles from these two infants, and electron microscopy of alveolar type 2 cells demonstrated abnormal lamellar body formation characteristic of this disorder.
ABCA3 mutations were the basis for lung disease in all three patients. Children with lung disease due to ABCA3 deficiency may not have symptoms at birth. The finding of five novel mutations indicates allelic heterogeneity for ABCA3 mutations within the Norwegian population.
调查三名挪威足月儿的难治性呼吸窘迫综合征是否由ABCA3基因突变所致。
对一名婴儿以及另外两名患有致命性新生儿肺部疾病的无关婴儿的父母进行编码表面活性蛋白B（SFTPB）、表面活性蛋白C（SFTPC）和ABCA3（ABCA3）的基因测序。通过组织学、免疫组织化学和电子显微镜检查肺组织。
在每个家庭中均鉴定出新型ABCA3突变。一名患者的表型与该疾病先前的描述不同，最初病情平稳。通过分析父母的DNA材料在死后19年确诊，在每位父母的一个等位基因上鉴定出ABCA3突变。另外两名婴儿有更典型的临床病程，出生后立即出现呼吸道症状。在这两名婴儿的两个等位基因上均鉴定出ABCA3突变，对Ⅱ型肺泡细胞的电子显微镜检查显示出该疾病特征性的异常板层小体形成。
ABCA3突变是所有三名患者肺部疾病的基础。因ABCA3缺乏导致肺部疾病的儿童出生时可能没有症状。发现五个新突变表明挪威人群中ABCA3突变存在等位基因异质性。
