NONSENSE MUTATION R1162X OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE DOES NOT REDUCE MESSENGER-RNA EXPRESSION IN NASAL EPITHELIAL TISSUE

Cystic fibrosis (CF) patients bearing the premature translation termin ation mutation (nonsense mutation) W1282X present severe pulmonary and pancreatic disease, whereas patients carrying other nonsense mutation s such as G542X, R553X, S1255X, R1162X, and W1316X show a severe pancr eatic but mild pulmonary illness. CF gene expression was found absent in respiratory tissues with mutations R553X and W1316X, which led to t he hypothesis that the absence of the gene product in the lung is more favorable than the presence of an altered one. We asked whether or no t all the nonsense mutations characterized by mild pulmonary disease p henotypes do present the absence of CF gene expression. We therefore i nvestigated gene expression at the mRNA level in respiratory cells obt ained from nasal polyps from a patient homozygous for the R1162X mutat ion. Gene expression was studied by amplification with polymerase chai n reaction of segments of the CF transmembrane conductance regulator c DNA that was obtained by reverse transcription of RNA. Semiquantitativ e analysis was performed by Northern analysis. By comparing the data o btained from polyps deriving from non-CF subjects and a CF patient hom ozygous for dF508 mutation, it is shown that no reduction of CF gene e xpression is evident in R1162X respiratory tissue. We conclude that CF nonsense mutations have heterogeneous mechanisms of gene expression.