Lung involvement, the delta F508 mutation and DNA haplotype analysis in cystic fibrosis

Abstract

Molecular studies of cystic fibrosis (CF) have allowed the genetic analysis of patients by means of DNA markers and the direct analysis of the CF gene. Some limited observations are available on the correlation between phenotype and genotype. Here, we report a study on the correlation of DNA haplotypes identified by KM-19 and XV-2c, the presence of the delta F508 mutation and lung involvement in 82 unrelated CF patients. Pulmonary involvement was defined by Chrispin's chest X-ray score, pulmonary function, sputum microbiology, serum immunoglobulin (SIg) levels and Shwachman's clinical score. Patients homozygous for haplotype B showed worse X-ray and clinical scores, more frequent sputum colonization by Pseudomonas aeruginosa and Staphylococcus aureus, lower spirometric values and raised concentrations of SIg G, A and M, compared with patients with other haplotypes. When lung involvement parameters were examined in patients homozygous, heterozygous or null for the delta F508 mutation, no difference was found among the three groups. Our data indicate a significant occurrence of severe pulmonary involvement in patients homozygous for the B haplotype; this is not influenced by the delta F508 mutation. We suggest that simple DNA haplotypes may provide data of both diagnostic and prognostic value, without the need for extensive and expensive molecular analyses.