NONSENSE MUTATION R1162X OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE DOES NOT REDUCE MESSENGER-RNA EXPRESSION IN NASAL EPITHELIAL TISSUE
R. Rolfini et G. Cabrini, NONSENSE MUTATION R1162X OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE DOES NOT REDUCE MESSENGER-RNA EXPRESSION IN NASAL EPITHELIAL TISSUE, The Journal of clinical investigation, 92(6), 1993, pp. 2683-2687
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.