title: Genotype-phenotype correlation in cystic fibrosis patients compound heterozygous for the A455E mutation.
abstract: Cystic fibrosis (CF) has a high incidence in the French-Canadian population of Saguenay Lac-Saint-Jean (Quebec). The A455E mutation accounts for 8.3% of the CF chromosomes. This mutation was shown to be associated with a milder lung disease in the Dutch population. Twenty two CF patients distributed in 17 families and compound heterozygotes for the A455E mutation have been followed at the Clinique de Fibrose Kystique de Chicoutimi. Fourteen patients also carried the delta F508 mutation while the remaining eight patients had the 621 + 1G-->T mutation. Each patient was matched by sex and age to a patient homozygous for the delta F508 mutation. The pairs were analyzed for several clinical and laboratory variables. The A455E compound heterozygotes were diagnosed at a later age (P = 0.003) and had chloride concentrations at the sweat test lower than those homozygous for the delta F508 mutation (P = 0.007). More patients were pancreatic sufficient (P = 0.004). They had a higher Shwachman score (P = 0.001) and better pulmonary function tests (P < 0.02). CF patients compound heterozygous for the A455E mutation have a milder pancreatic and lung disease than the delta F508 homozygotes. Therefore, the A455E should be associated with a better prognosis.
authors.affiliation: Département des Sciences Humaines Université du Québec à Chicoutimi, Canada.
authors.forename: M
authors.initials: M
authors.lastname: De Braekeleer
authors.forename: C
authors.initials: C
authors.lastname: Allard
authors.forename: J P
authors.initials: JP
authors.lastname: Leblanc
authors.forename: F
authors.initials: F
authors.lastname: Simard
authors.forename: G
authors.initials: G
authors.lastname: Aubin
mesh_terms: D000293:Adolescent; D000328:Adult; D002170:Canada; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D010188:Exocrine Pancreatic Insufficiency / Q000150:complications / Q000235:genetics; D005260:Female; D005602:France / Q000208:ethnology; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D009154:Mutation; D010641:Phenotype; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric; D013542:Sweat / Q000737:chemistry
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator