Genotype Analysis and Phenotypic Manifestations of Children With Intermediate Sweat Chloride Test Results

摘要

Study objectives: Cystic fibrosis (CF) is one of the most common inherited diseases among whites.nSince the cloning of the CF transmembrane conductance regulator (CFTR) gene, a number ofnstudies have focused on associations between the genotype and phenotype in CF. This had led tonthe progressive identification of new groups of patients, including those who have mild lungndisease and those who have normal sweat chloride values (< 60 mEq/L). The aim of the presentnwork was to provide information on the genotype and the phenotypic characteristics of childrennwith intermediate-range sweat chloride test results.nPatients and results: We focused on children referred to the pulmonary department for variousntypes of pulmonary disease and who had several sweat chloride test results with median values innthe range of 40 to 60 mEq/L. Twenty-four patients over a 10-year period were enrolled (meannage, 4.8 years). Respiratory manifestations at initial evaluation included recurrent bronchitis,nwheezing, chronic cough, and pneumonia. The duration of the follow-up ranged from 0.5 to 10.5nyears. Sputum cultures revealed the presence of Haemophilus influenzae (10 children), Staphylococcusnaureus (4 children), and Pseudomonas aeruginosa (3 children). Pancreatic insufficiencynwas found in two patients. Analysis of the entire coding sequence allowed identification of 16nknown mutations in CFTR gene. Fifteen chromosomes (31.2%) carried a mutation in CFTR genenand one allele carried two mutations. Three patients were homozygous or double heterozygousn(DF508/DF508, DF508/3849 1 10 kb C3T, S1235R/G551D). The 5-thymidine allele was identifiednin four children.nConclusion: These results indicate an higher frequency of CFTR gene mutations in patients withnborderline sweat chloride test results, compared to data reported in the general population. Theynlead to the recommendations for complete pulmonary and GI investigations in this group ofnpatients, as well as assiduous care and medical follow-up.