title: Missense mutations in the cystic fibrosis gene in adult patients with asthma.
abstract: Asthma is a complex genetic disorder that affects 5% of adults and 10% of children worldwide. The complete characterization of the cystic fibrosis transmembrane conductance regulator (CFTR) gene identified missense mutations in 15% of 144 unrelated adult patients with asthma, but in none of 41 subjects from the general population. The four more common mutations were analyzed in an extended sample consisting of 184 individuals from the general population and did not show a significant difference in frequency. The hyperfunctional CFTR M470 allele was detected in 90% of patients with CFTR missense mutations, but in 63% of subjects from the general population and 63% of asthma patients without CFTR mutations. None of the patients with missense mutations had the 5T allele of intron 8 of CFTR, responsible for low CFTR levels, while it was detected in 8% of asthma patients without CFTR mutations and in 9% of subjects from the general population. These findings suggest a putative role for a combination of CFTR missense mutations, including the M470 allele, in the genetic variability of asthma.
authors.affiliation: Medical and Molecular Genetics Center-IRO, Hospital Duran i Reynals, L' Hospitalet, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Lázaro
authors.forename: R
authors.initials: R
authors.lastname: de Cid
authors.forename: J
authors.initials: J
authors.lastname: Sunyer
authors.forename: J
authors.initials: J
authors.lastname: Soriano
authors.forename: J
authors.initials: J
authors.lastname: Giménez
authors.forename: M
authors.initials: M
authors.lastname: Alvarez
authors.forename: T
authors.initials: T
authors.lastname: Casals
authors.forename: J M
authors.initials: JM
authors.lastname: Antó
authors.forename: X
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator