Genotype/phenotype correlation of the G85E mutation in a large cohort of cystic fibrosis patients.
In this European study, the phenotype in 68 patients, homozygous or compound heterozygous for the G85E mutation, was investigated. Each index case was compared with two cystic fibrosis (CF) patients from the same clinic, matched for age and sex: one with pancreatic sufficiency (PS) and one with pancreatic insufficiency (PI). When comparing 31 G85E/F508del and F508del/F508del patients, there were no differences in median age at diagnosis, mean sweat chloride value, most recent weight for height, most recent forced expiratory volume in one second % predicted, prevalence of chronic Pseudomonas aeruginosa colonisation and typical CF complications. However, PI was less frequent in the G85E/F508del group. Comparison of 55 G85E patients (with second mutation known and not classified as mild) with PS controls (n=44) showed that the G85E patients had a significantly higher sweat chloride, more often failure to thrive at diagnosis, higher prevalence of PI, worse current weight for height, higher prevalence of chronic P. aeruginosa colonisation and liver cirrhosis. Pulse-chase experiments revealed that G85E cystic fibrosis transmembrane conductance regulator failed to mature on a M470 as well as on a V470 background. Therefore, G85E is a class II mutation. Although there is variability in its clinical presentation, G85E mutation results in a severe phenotype.
Decaestecker
K
K
Dept of Pediatrics, University of Leuven, Leuven, Belgium.
Decaestecker
E
E
Castellani
C
C
Jaspers
M
M
Cuppens
H
H
De Boeck
K
K
D000293:Adolescent; D000328:Adult; D000818:Animals; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D010188:Exocrine Pancreatic Insufficiency / Q000453:epidemiology / Q000209:etiology; D017353:Gene Deletion; D005838:Genotype; D018698:Glutamic Acid; D005998:Glycine; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015994:Incidence; D009154:Mutation; D010179:Pancreas / Q000503:physiopathology; D010641:Phenotype; D035781:Siblings
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D018698:Glutamic Acid; D005998:Glycine