title: CFTR genotypes in patients with normal or borderline sweat chloride levels.
abstract: In recent years, some patients bearing "atypical" forms of cystic fibrosis (CF) with normal sweat chloride concentrations have been described. To identify the spectrum of mutant combinations causing such atypical CF, we collected the results of CFTR (ABCC7) mutation analysis from 15 laboratories. Thirty patients with one or more typical symptoms of the disease associated with normal or borderline sweat chloride levels and bearing two CFTR mutations were selected. Phenotypes and genotypes of these 30 patients are described. A total of 18 different CFTR mutations were observed in the 60 chromosomes analysed. F508del was present in 31.6 % of the mutated chromosomes and 3849+10kbC>T in 13.3 %. R117H, D1152H, L206W, 3272-26A>G, S1235R, G149R, R1070W, S945L, and the poly-T tract variation commonly called IVS8-5T were also observed. The relative frequency of CFTR mutations clearly differed from that observed in typical CF patients or in CBAVD patients with the same ethnic origin. A mild genotype with one or two mild or variable mutations was observed in all the patients. These findings improve our understanding of the distribution of CFTR alleles in CF with normal or borderline sweat chloride concentrations and will facilitate the development of more sensitive CFTR mutation screening.
authors.affiliation: Laboratoire de Biochimie, Hôpital A. Trousseau, AP-HP, Paris, France. delphine.feldmann@trs.ap-hop-paris.fr
authors.forename: Delphine
authors.initials: D
authors.lastname: Feldmann
authors.forename: Remy
authors.initials: R
authors.lastname: Couderc
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Audrezet
authors.forename: Claude
authors.initials: C
authors.lastname: Ferec
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
authors.forename: Marie
authors.initials: M
authors.lastname: Desgeorges
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Hervé
authors.initials: H
authors.lastname: Mittre
authors.forename: Martine
authors.initials: M
authors.lastname: Blayau
authors.forename: Dominique
authors.initials: D
authors.lastname: Bozon
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Malinge
authors.forename: Nicole
authors.initials: N
authors.lastname: Monnier
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bonnefont
authors.forename: Albert
authors.initials: A
authors.lastname: Iron
authors.forename: Eric
authors.initials: E
authors.lastname: Bieth
authors.forename: Viviane
authors.initials: V
authors.lastname: Dumur
authors.forename: Christine
authors.initials: C
authors.lastname: Clavel
authors.forename: Cécile
authors.initials: C
authors.lastname: Cazeneuve
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Girodon
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002712:Chlorides / Q000032:analysis; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D013542:Sweat / Q000737:chemistry
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator