CFTR genotypes in patients with normal or borderline sweat chloride levels.
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.
Feldmann
Delphine
D
Laboratoire de Biochimie, Hôpital A. Trousseau, AP-HP, Paris, France. delphine.feldmann@trs.ap-hop-paris.fr
Couderc
Remy
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Audrezet
Marie-Pierre
MP
Ferec
Claude
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Bienvenu
Thierry
T
Desgeorges
Marie
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Claustres
Mireille
M
Mittre
Hervé
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Blayau
Martine
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Bozon
Dominique
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Malinge
Marie-Claire
MC
Monnier
Nicole
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Bonnefont
Jean-Paul
JP
Iron
Albert
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Bieth
Eric
E
Dumur
Viviane
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Clavel
Christine
C
Cazeneuve
Cécile
C
Girodon
Emmanuelle
E
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
C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator