title: Phenotypic expression of genotype-phenotype correlation in cystic fibrosis patients carrying the 852del22 mutation.
abstract: 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 DeltaF508 mutation [n = 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 = NS), estimated time needed to develop a severe lung disease (22.1 vs. 24.5 years; P = 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 DeltaF508 and, as in the latter case, there is no strict genotype/phenotype correlation.
authors.affiliation: Dipartimento di Biomedicina dell'Età Evolutiva, Sezione di Pediatria Clinica e Sociale, Università di Bari, Bari, Italy. a.polizzi@pediatria2.uniba.it
authors.forename: Angela
authors.initials: A
authors.lastname: Polizzi
authors.forename: Ruggiero
authors.initials: R
authors.lastname: Francavilla
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castaldo
authors.forename: Teresa
authors.initials: T
authors.lastname: Santostasi
authors.forename: Rossella
authors.initials: R
authors.lastname: Tomaiuolo
authors.forename: Antonio
authors.initials: A
authors.lastname: Manca
authors.forename: Francesco
authors.initials: F
authors.lastname: De Robertis
authors.forename: Luigi
authors.initials: L
authors.lastname: Mappa
authors.forename: Francesca Paola
authors.initials: FP
authors.lastname: Oliverio
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.forename: Nicola
authors.initials: N
authors.lastname: Rigillo
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D015992:Body Mass Index; D016956:Burkholderia cepacia / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D017384:Sequence Deletion; D013183:Sputum / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA