Surfactant protein C mutations in sporadic forms of idiopathic interstitial pneumonias

Abstract

Interstitial pneumonias have recently been associated with mutations in the gene encoding surfactant protein C (SFTPC). In particular, SFTPC mutations have been reported in a number of familial forms of pulmonary fibrosis and in infants with interstitial lung diseases. The present study searched for SFTPC mutations in adult patients with sporadic idiopathic interstitial pneumonia.In total, 35 adult patients with sporadic idiopathic interstitial pneumonia and 50 healthy subjects were investigated for SFTPC mutations by direct DNA sequencing. Of the patients with sporadic idiopathic interstitial pneumonia, 25 suffered from idiopathic pulmonary fibrosis and 10 patients from nonspecific interstitial pneumonia.Only two frequent nonsynonymous variants, T138N and S186N, were detected. Allele frequencies of both variations as well as of other identified noncoding alterations did not differ significantly between the diverse patient groups and control subjects.In conclusion, mutations in the gene encoding surfactant protein C are not common in sporadic cases of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia, suggesting that the mutated gene does not play an important role in the pathogenesis of these forms of idiopathic interstitial pneumonia.

Epithelial Endoplasmic Reticulum Stress and Apoptosis in Sporadic Idiopathic Pulmonary Fibrosis

“…In contrast to familial forms of IIP, no mutations of the SFTPC gene have been found in sporadic IPF or nonspecific interstitial pneumonia (15,16). The origin of the observed AECII death in sporadic IPF therefore remains elusive.…”

Genetics and Early Detection in Idiopathic Pulmonary Fibrosis

“…For example, heterozygous mutations of the surfactant protein C gene (SFTPC) were originally described in 2001 in a case of familial interstitial pneumonia, including in an infant who was diagnosed with NSIP and whose mother had DIP (43). Since that time, multiple other mutations in SFTPC have been described in children, which have been noted to cause NSIP, DIP, and pulmonary alveolar proteinosis (44)(45)(46)(47)(48), whereas adults with similar mutations are often diagnosed with IPF and to a lesser degree NSIP and unclassified fibrosis (44,(49)(50)(51)(52)(53) (32,(54)(55)(56) may confer an increase in the risk of UIP; however, some of these studies have also included additional histopathologic forms of IIP in their analyses (32,(54)(55)(56). In summary, although the extent of histopathologies associated with the MUC5B variant have not been assessed to date, the data from genetic variants of SFTPC and for multiple genes controlling telomere length suggest that the MUC5B variant might be expected to increase the risk for multiple histopathologies in addition to UIP.…”

A novel surfactant protein C L55F mutation associated with interstitial lung disease alters subcellular localization of proSP-C in A549 cells

“…The patient's mother and several volunteers also possessed substitutions of c.413C>A and c.557G>A, which have been described as common coding SNPs in previous studies (14). Paternal gene sequences were identical to those of healthy control volunteers.…”