Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations
Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations
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DOI：
10.1007/s00431-013-1977-8
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发表时间：
2013-07-01
影响因子：
3.6
通讯作者：
Kure, Shigeo
中科院分区：
文献类型：
--
作者：
Kitazawa, Hiroshi;Moriya, Kunihiko;Kure, Shigeo
表面活性物质代谢的关键基因突变，包括表面活性蛋白C（SP-C）和ABCA 3，是间质性肺病的公认原因。ABCA 3的隐性突变首先归因于足月新生儿的致命性呼吸衰竭，但它们也越来越多地被认为是年龄较大的儿童和成人中不太严重表型的呼吸系统疾病的原因。在这里，我们报告一个20个月大的男孩与间质性肺病引起的两个不同的ABCA 3突变。甲基强的松龙的初步治疗不成功，但额外给予羟氯喹有效。家族史显示，患者的哥哥在6个月大时死于特发性间质性肺病，提示该疾病的遗传病因。SP-C和ABCA 3基因的序列分析使用来自患者本人、其父母和其兄弟的DNA样本进行。这些分析揭示了患者和他兄弟的ABCA 3编码外显子中的新型复合杂合突变：c.2741A > G，父亲起源，和c.3715_3716insGGGGGG，母亲起源。结论ABCA 3基因突变是一个异质性的实体，具有多种表型，因此我们建议对不明原因间质性肺疾病患儿进行SP-C和ABCA 3基因突变的基因检测。
Mutations in genes critical for surfactant metabolism, including surfactant protein C (SP-C) and ABCA3, are well-recognized causes of interstitial lung disease. Recessive mutations in ABCA3 were first attributed to fatal respiratory failure in full-term neonates, but they are also increasingly being recognized as a cause of respiratory disorders with less severe phenotypes in older children and also adults. Here, we report a 20-month-old boy with interstitial lung disease caused by two distinct ABCA3 mutations. Initial treatment with methylprednisolone was unsuccessful, but the additional administration of hydroxychloroquine was effective. The family history revealed that the patient's older brother had died of idiopathic interstitial lung disease at 6 months of age, suggesting a genetic etiology of the disease. Sequence analyses of SP-C and ABCA3 genes were performed using DNA samples from the patient himself, his parents, and his brother. These analyses revealed novel compound heterozygous mutations in the coding exons of ABCA3 in both the patient and his brother: c.2741A > G, of paternal origin, and c.3715_3716insGGGGGG, of maternal origin. Conclusion Since ABCA3 mutations seem to be a heterogeneous entity with various phenotypes, we recommend genetic testing for mutations in SP-C and ABCA3 genes to be considered in children with unexplained interstitial lung disease.