Missense mutation R1066C in the second transmembrane domain of CFTR causes a severe cystic fibrosis phenotype: Study of 19 heterozygous and 2 homozygous patients

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 ΔF508/ΔF508 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 ΔF508/ΔF508 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 ΔF508/ΔF508 group (57.5%). Other clinical complications were significantly more frequent in the R1066C/any mutation patients(P < 0.02) than in the ΔF508/ΔF508 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 ΔF508 patients. The poor clinical scores and complications of patients with the R1066C mutation are probably related to their slightly longer survival. Hum Mutat 10:387–392, 1997. © 1997 Wiley‐Liss, Inc.