Correlation of sweat chloride concentration with classes of the cystic fibrosis transmembrane conductance regulator gene mutations

• Published in: The Journal of pediatrics Vol. 127; no. 5; pp. 705 - 710
• Main Authors: Wilschanski, Michael, Zielenski, Julian, Markiewicz, Danuta, Tsui, Lap-Chee, Corey, Mary, Levison, Henry, Durie, Peter R.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.11.1995; Elsevier
• Subjects: Biological and medical sciences; Child; Child, Preschool; Chlorides - analysis; Cystic Fibrosis - classification; Cystic Fibrosis - genetics; Cystic Fibrosis - metabolism; Cystic Fibrosis Transmembrane Conductance Regulator - classification; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Errors of metabolism; Genes, Regulator - genetics; Genotype; Heterozygote; Homozygote; Humans; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Mutation; Phenotype; Retrospective Studies; Sweat - chemistry; CF; NBF; PS; RT-PCR; PI; cAMP; CFTR; Human; Correlation; Respiratory disease; Metabolic diseases; Genotype; Cystic fibrosis; Ionic channel; Genetic disease; Phenotype; Gene; Chlorides; Classification; Digestive diseases; Ionic conductance; Mutation; Sweat; Pancreatic disease
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/S0022-3476(95)70157-5

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 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. Conclusion: Studies of differences in chloride conductance between functional classes of CFTR mutations provide insight into phenotypic expression of the disease. (J P EDIATR 1995;127:705-10)