Phenotypic expression of genotype-phenotype correlation in cystic fibrosis patients carrying the 852del22 mutation

Currently, more than 1,000 mutations have been
identified in the cystic fibrosis transmembrane
regulator (CFTR) gene. While some mutations are
common worldwide, the majority are restricted
in certain ethnic groups. We have found that in
Southern Italy, the 852del22 mutation is well
represented with a frequency of 3.5%. We have
screened, by reverse dot blot, denaturing gradient
gel electrophoresis (DGGE), and gene sequencing,
the entire coding regions of CFTR gene in 371
consecutive cystic fibrosis (CF) patients from
Southern Italy and have identified 17 patients
carrying rare genotypes, among which 13 [6 M;
median age 21.7 years (range: 4.5–47.7 years)]
carry the 852del22 mutation. To assess the phenotypic expression of CF in patients with the
852del22 mutations we have compared these
patients with a group of age and gender matched
patients homozygous for the DF508 mutation
[n ¼ 34; 19 M; median age 19.9 years (range: 3.8–
34.6 years)]. Overall, we found no difference in
terms of complications, patient survival (17.6% vs.
30.7%; P ¼ NS), estimated time needed to develop a
severe lung disease (22.1 vs. 24.5 years; P ¼ NS),
nutritional status, and rate of infection or colonization by most common pathogens between
patients in the two groups. Finally, we have found
that a late diagnosis was associated with a poor
outcome (severe lung disease) regardless of genotype. Our data show that 852del22 mutation
results in a phenotypic expression of disease as
severe as that determined by the more typical
DF508 and, as in the latter case, there is no strict
genotype/phenotype correlation