A novel surfactant protein C mutation resulting in aberrant protein processing and altered subcellular localization causes infantile interstitial lung disease

作者：Hong, Da; Qi, Yuanyuan; Liu, Jing; Wang, Huijun; Wang, Libo; Qian, Liling^*

来源：Pediatric Research, 2017, 81(6): 891-897.

DOI：10.1038/pr.2017.29

• ENDOPLASMIC-RETICULUM STRESS
• EPITHELIAL-CELLS
• DEGRADATION
• ACTIVATION
• MECHANISMS
• PROMOTES
• CHILDREN
• PATHWAY

BACKGROUND: Mutations in the surfactant protein C gene (SFTPC) result in interstitial lung disease (ILD). Our objective was to report a novel SFTPC mutation and evaluate the effect of this mutant on protein synthesis and processing.
METHODS: Genomic DNA was extracted from whole blood of a Chinese infant with ILD and candidate genes associated with ILD were sequenced by next-generation sequencing. Subclones of wild-type and mutant SFTPC were transiently transfected into A549 cells. The functional characterization of mutant surfactant protein C (SP-C) was evaluated by Western blotting, transmission electron microscopy, and immunofluorescence.
RESULTS: A novel heterozygous mutation SFTPC: c.337T>T/C, p.Y113H was identified in this ILD infant. Neither of the parents carries this mutation. Using A549 cells expressing wild type and mutant SP-C isoforms, Western blotting revealed a significant reduction of proSP-C and a band with abnormal molecular weight in the mutant SP-C compared to the wild type. Ultrastructural analysis showed abnormal cytoplasmic organelles. Immunofluorescence demonstrated mutant SP-C was scarcely trafficked to lamellar bodies but localized well to early endosomes, which was in marked contrast to the wild type protein.
CONCLUSION: We detected a novel mutation in SFTPC causing ILD in infancy. The mutation results in aberrant proSP-C processing and altered subcellular localization.

• 出版日期2017-6
• 单位复旦大学