Patients with mutations in the pulmonary surfactant protein C (SP-C) gene develop interstitial lung disease and pulmonary exacerbations associated with viral infections including respiratory syncytial virus (RSV).
Mutations in the surfactant protein C gene (SFTPC) have been recently associated with the development of diffuse lung disease, particularly sporadic and familial interstitial lung disease (ILD).
In general, mutations in the SP-B gene SFTPB are associated with fatal respiratory distress in the neonatal period, and mutations in the SP-C gene SFTPC are more commonly associated with interstitial lung disease in older infants, children, and adults.
More than 20 mutations in the ER-lumenal CTC (C-terminal domain of proSP-C), are associated with ILD (interstitial lung disease), and some of the mutations cause intracellular accumulation of cytotoxic protein aggregates and a corresponding decrease in mature SP-C.
Recessive loss-of-function mutations in the surfactant protein-B and the ATP-binding cassette family member A3 (ABCA3) genes present as lethal surfactant deficiency in the newborn, whereas other recessive mutations in ABCA3 and dominant mutations in the surfactant protein-C gene result in interstitial lung disease in older infants and children.
The wide variability in the age of onset of ILD in patients with SFTPC mutations may be related to environmental insults that ultimately overwhelm the homeostatic cytoprotective response.
Recessive loss of function mutations in surfactant protein-B (SP-B) gene lead to respiratory failure that is lethal in the newborn period while single allelic mutations in the surfactant protein-C (SP-C) gene cause interstitial lung disease of varying severity and age of onset.
There is growing evidence that mutations in the surfactant protein C gene play a role in the pathogenesis of certain forms of pediatric interstitial lung disease.
The E66K substitution is representative of a new class of SP-C mutation associated with interstitial lung disease that is diverted from the normal biosynthetic pathway.
This review examines the current state of SP-C biosynthesis with a focus on recent developments related to molecular and cellular mechanisms implicated in the emerging role of SP-C mutations in the pathophysiology of diffuse parenchymal lung disease.
The I73T mutation was found on 7 of 232 SP-C alleles from 7 unrelated children with ILD but was not found on 332 control SP-C alleles ( P < .01, Fisher exact test).
Mutations in the gene encoding SP-B result in severe, fatal neonatal lung disease, and mutations in the gene encoding SP-C are associated with chronic interstitial lung diseases in newborns, older children, and adults.
Recently, two seemingly dominant-negative mutations of the pro-SP-C-encoding gene (SFTPC, MIM 178620), were reported in families with vertically-inherited interstitial lung disease (Nogee et al.
These observations suggest that individuals with this particular mutation in surfactant protein C gene might be at increased risk of interstitial lung disease of variety of types.
To determine the effects of a mutation in the SP-C gene on surfactant, we obtained lung tissue at the time of transplantation from a 14-mo-old infant with progressive ILD.
These observations suggest that individuals with this particular mutation in surfactant protein C gene might be at increased risk of interstitial lung disease of variety of types.
Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred.
Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD.