Correlation of sweat chloride concentration with classes of the cystic fibrosis transmembrane conductance regulator gene mutations.
OBJECTIVE
To compare differences in epithelial chloride conductance according to class of mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.


METHODS
We evaluated the relationship between the functional classes of CFTR mutations and chloride conductance using the first diagnostic sweat chloride concentration in a large cystic fibrosis (CF) population.


RESULTS
There was no difference in sweat chloride value value between classes of CFTR mutations that produce no protein (class I), fail to reach the apical membrane because of defective processing (class II), or produce protein that fails to respond to cyclic adenosine monophosphate (class III). Those mutations that produce a cyclic adenosine monophosphate-responsive channel with reduced conductance (class IV) were associated with a significantly lower, intermediate sweat chloride value. However, patients with the mutations that cause reduced synthesis or partially defective processing of normal CFTR (class V) had sweat chloride concentrations similar to those in classes I to III.


CONCLUSIONS
Studies of differences in chloride conductance between functional classes of CFTR mutations provide insight into phenotypic expression of the disease.
D002648:Child; D002675:Child, Preschool; D002712:Chlorides / Q000032:analysis*; D003550:Cystic Fibrosis / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000145:classification / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies; D013542:Sweat / Q000737:chemistry*
C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator