Pneumology Unit, IRCCS San Matteo Foundation Hospital, Piazza Golgi 1, Pavia 27100, Italy.
Respir Res. 2014 Apr 15;15(1):43. doi: 10.1186/1465-9921-15-43.
Interstitial lung disease occurring in children is a condition characterized by high frequency of cases due to genetic aberrations of pulmonary surfactant homeostasis, that are also believed to be responsible of a fraction of familial pulmonary fibrosis. To our knowledge, ABCA3 gene was not previously reported as causative agent of fibrosis affecting both children and adults in the same kindred.
We investigated a large kindred in which two members, a girl whose interstitial lung disease was first recognized at age of 13, and an adult, showed a diffuse pulmonary fibrosis with marked differences in terms of morphology and imaging. An additional, asymptomatic family member was detected by genetic analysis. Surfactant abnormalities were investigated at biochemical, and genetic level, as well as by cell transfection experiments.
Bronchoalveolar lavage fluid analysis of the patients revealed absence of surfactant protein C, whereas the gene sequence was normal. By contrast, sequence of the ABCA3 gene showed a novel homozygous G > A transition at nucleotide 2891, localized within exon 21, resulting in a glycine to aspartic acid change at codon 964. Interestingly, the lung specimens from the girl displayed a morphologic usual interstitial pneumonitis-like pattern, whereas the specimens from one of the two adult patients showed rather a non specific interstitial pneumonitis-like pattern.
We have detected a large kindred with a novel ABCA3 mutation likely causing interstitial lung fibrosis affecting either young and adult family members. We suggest that ABCA3 gene should be considered in genetic testing in the occurrence of familial pulmonary fibrosis.
儿童发生的间质性肺病是一种以肺表面活性剂稳态遗传异常导致的高频率发病为特征的疾病，这些遗传异常也被认为是家族性肺纤维化的一部分原因。据我们所知，ABCA3 基因以前没有被报道为导致同一家族中的儿童和成人都发生纤维化的原因。
我们研究了一个大家庭，其中两名成员，一名女孩在 13 岁时首次被诊断为间质性肺病，一名成年患者表现为弥漫性肺纤维化，在形态和影像学上有明显差异。通过基因分析检测到另一名无症状的家族成员。在生化、基因水平以及通过细胞转染实验研究了表面活性剂异常。
患者的支气管肺泡灌洗液分析显示表面活性蛋白 C 缺失，而基因序列正常。相比之下，ABCA3 基因的序列显示第 2891 位核苷酸的新型纯合 G > A 转换，导致 964 位密码子的甘氨酸变为天冬氨酸。有趣的是，女孩的肺标本显示出通常的间质性肺炎样形态，而两名成年患者之一的标本显示出非特异性间质性肺炎样形态。
我们发现了一个有新的 ABCA3 突变的大家庭，这种突变可能导致影响年轻和成年家庭成员的间质性肺纤维化。我们建议在家族性肺纤维化发生时，应考虑进行 ABCA3 基因的基因检测。
