A common mutation in the surfactant protein C gene associated with lung disease

Objective: To determine the contribution of the surfactant protein C (SP-C) I73T mutation to lung disease. Study design: Genomic DNA was obtained from 116 children with interstitial lung disease (ILD) or chronic lung disease of unclear cause and from 166 control subjects and was screened for the I73T mutation using an allele-specific polymerase chain reaction assay. Results: 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). The I73T mutation segregated with lung disease in one kindred with familial ILD. The I73T mutation was found in an asymptomatic parent from two different families with affected children consistent with variable penetrance, but it was not found in either asymptomatic parent of two other unrelated affected children consistent with a de novo mutation. Analysis of single nucleotide polymorphisms indicated diverse genetic backgrounds of the I73T alleles. Immunohistochemical analysis of lung tissue from an infant with the I73T mutation demonstrated normal staining patterns for proSP-B, SP-B, and proSP-C. Conclusions: These findings support the hypothesis that the I73T mutation predisposes to or causes lung disease.