title: Comprehensive cystic fibrosis mutation epidemiology and haplotype characterization in a southern Italian population.
abstract: We screened the whole coding region of the cystic fibrosis transmembrane regulator (CFTR) gene in 371 unrelated cystic fibrosis (CF) patients from three regions of southern Italy. Forty-three mutations detected 91.5% of CF mutated chromosomes by denaturing gradient gel electrophoresis analysis, and three intragenic CFTR polymorphisms predicted a myriad of rare mutations in uncharacterized CF chromosomes. Twelve mutations are peculiar to CF chromosomes from southern Italy: R1158X, 4016insT, L1065P and 711 + 1G > T are present in 6.3% of CF chromosomes in Campania; G1244E and 852del22 are present in 9.6% of CF chromosomes in Basilicata and 4382delA, 1259insA, I502T, 852del22, 4016insT, D579G, R1158X, L1077P and G1349D are frequent in Puglia (19.6% of CF alleles). Several mutations frequently found in northern Italy (e.g., R1162X, 711 + 5G > T) and northern Europe (e.g., G551D, I507del and 621 + 1G > T) are absent from the studied population. The I148T-3195del6 complex allele was present in two CF chromosomes, whereas I148T was present in both alleles (as a single mutation) in another CF patient and in five CF carriers; this could result from crossover events. The haplotype analysis of three intragenic polymorphisms (IVS8CA, IVS17bTA and IVS17bCA) compared with data from other studies revealed that several mutations (3849 + 10kbC > T, 1717-1G > A, E585X, 3272-26G > A, L558S, 2184insA and R347P) originated from multiple events, whereas others (R1158X and S549R) could be associated with one or more intragenic recombinant events. Given the large population migration from southern Italy, knowledge of the CF molecular epidemiology in this area is an important contribution to diagnosis, counselling and interlaboratory quality control for molecular laboratories worldwide.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, via Pansini 5, 1-80131 Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Castaldo
authors.forename: A
authors.initials: A
authors.lastname: Polizzi
authors.forename: R
authors.initials: R
authors.lastname: Tomaiuolo
authors.forename: C
authors.initials: C
authors.lastname: Cazeneuve
authors.forename: E
authors.initials: E
authors.lastname: Girodon
authors.forename: T
authors.initials: T
authors.lastname: Santostasi
authors.forename: D
authors.initials: D
authors.lastname: Salvatore
authors.forename: V
authors.initials: V
authors.lastname: Raia
authors.forename: N
authors.initials: N
authors.lastname: Rigillo
authors.forename: M
authors.initials: M
authors.lastname: Goossens
authors.forename: F
authors.initials: F
authors.lastname: Salvatore
mesh_terms: D003550:Cystic Fibrosis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005820:Genetic Testing; D006239:Haplotypes / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007558:Italy / Q000453:epidemiology; D017720:Molecular Epidemiology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator