Abstract
BackgroundMutations in the surfactant protein C gene (SFTPC) result in interstitial lung disease (ILD). Our objective was to characterize clinical and genetic spectrum of ILD in Chinese children associated with SFTPC mutations.MethodsSix Chinese children with ILD heterozygous for SFTPC mutations were included. Candidate genes responsible for surfactant dysfunction were sequenced by next-generation sequencing. Subclones of SFTPC with novel mutations were generated and transiently transfected into A549 cells. The functional characterization of mutant surfactant protein C (SP-C) was evaluated by Western blotting and immunofluorescence.ResultsThe age of onset ranged from 7 days to 15 months. All cases required supplemental oxygen. Failure to thrive (5/6) was the most significant extra-pulmonary manifestation. Hydroxychloroquine was given as the long-term treatment of lung disease in four patients and two of them responded well. Three mutations were identified in six patients: four with I73T, one with D105G, one with Y113H. Mutations in three patients were inherited and three arised de novo. Western blotting revealed totally different band patterns between mutant SP-C (D105G and Y113H) and the wildtype. Immunofluorescence showed mutant SP-C (D105G) was scarcely trafficked to lamellar bodies but localized well to early endosomes, which was in marked contrast to the wildtype protein.ConclusionSFTPC mutations were an important cause of childhood ILD in Chinese population. I73T was a common SFTPC mutation in Chinese ILD children associated with surfactant protein C mutations.
Highlights
Mutations in the surfactant protein C gene (SFTPC) result in interstitial lung disease (ILD)
With the increase of awareness of this disease and advances in diagnostic technique, rare, we discover that SFTPC mutations account for a substantial proportion of unexplained ILD with early onset in our Chinese population
The age at onset of patients with SFTPC mutations ranged from 7 days to 15 months which seems to be earlier than those without surfactant dysfunction
Summary
Mutations in the surfactant protein C gene (SFTPC) result in interstitial lung disease (ILD). Our objective was to characterize clinical and genetic spectrum of ILD in Chinese children associated with SFTPC mutations. Interstitial lung disease (ILD) in children represents a heterogeneous group of respiratory disorders that are characterized by impaired gas exchange and diffuse infiltrates [1]. Significant advances have been made in understanding the underlying causes for childhood ILD (chILD) such as genetic disorders of surfactant dysfunction which result from mutations in. Whether patients with different geographic and ethnic origins differ in clinical and genetic spectrum remains unclear. Chen J et al [11] reported 18 Chinese cases with surfactant dysfunction. We report the clinical features and genetic findings in 6 Chinese subjects heterozygous for SFTPC mutations to expand the genetic and clinical spectrum
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