title: Missense mutation R1066C in the second transmembrane domain of CFTR causes a severe cystic fibrosis phenotype: study of 19 heterozygous and 2 homozygous patients.
abstract: We report the clinical features of 21 unrelated cystic fibrosis (CF) patients from Portugal and Spain, who carry the mutation R1066C in the CFTR gene. The current age of the patients was higher in the R1066C/any mutation group (P < 0.01), as compared to the deltaF508/deltaF508 group. Poor values for lung radiological involvement (Chrispin-Norman) and general status (Shwachman-Kulcycki) were observed in the R1066C/any mutation group (P < 0.005 and P < 0.0004). A slightly, but not significantly worse lung function was found in the R1066C/any mutation group when compared with the deltaF508/deltaF508 patients. No significant differences were detected regarding the age at diagnosis, sweat Cl-values, or percentiles of height and weight between the two groups. Neither were significant differences observed regarding sex, meconium ileus (4.7% vs. 11.1%), dehydration (10.5% vs. 14.7%), or pancreatic insufficiency (PI) (100% vs. 97.8%). The proportion of patients with lung colonization by bacterial pathogens was slightly, but not significantly higher in the R1066C/any mutation group (70.0%), as compared with the deltaF508/deltaF508 group (57.5%). Other clinical complications were significantly more frequent in the R1066C/any mutation patients(P < 0.02) than in the deltaF508/deltaF508 group. The two homozygous R1066C/R1066C patients died at the ages of 3 months and 7 years. The data presented in this study clearly demonstrate that the R1066C mutation is responsible for a severe phenotype similar to that observed in homozygous deltaF508 patients. The poor clinical scores and complications of patients with the R1066C mutation are probably related to their slightly longer survival.
authors.affiliation: Molecular Genetics Department (IRO), Hospital Duran i Reynals, Barcelona, Catalonia, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Casals
authors.forename: P
authors.initials: P
authors.lastname: Pacheco
authors.forename: C
authors.initials: C
authors.lastname: Barreto
authors.forename: J
authors.initials: J
authors.lastname: Giménez
authors.forename: M D
authors.initials: MD
authors.lastname: Ramos
authors.forename: S
authors.initials: S
authors.lastname: Pereira
authors.forename: J A
authors.initials: JA
authors.lastname: Pinheiro
authors.forename: N
authors.initials: N
authors.lastname: Cobos
authors.forename: A
authors.initials: A
authors.lastname: Curvelo
authors.forename: C
authors.initials: C
authors.lastname: Vázquez
authors.forename: H
authors.initials: H
authors.lastname: Rocha
authors.forename: J L
authors.initials: JL
authors.lastname: Séculi
authors.forename: E
authors.initials: E
authors.lastname: Pérez
authors.forename: J
authors.initials: J
authors.lastname: Dapena
authors.forename: E
authors.initials: E
authors.lastname: Carrilho
authors.forename: A
authors.initials: A
authors.lastname: Duarte
authors.forename: A M
authors.initials: AM
authors.lastname: Palacio
authors.forename: V
authors.initials: V
authors.lastname: Nunes
authors.forename: J
authors.initials: J
authors.lastname: Lavinha
authors.forename: X
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004276:DNA, Satellite; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: C505032:CFTR protein, human; D004276:DNA, Satellite; D019005:Cystic Fibrosis Transmembrane Conductance Regulator