Lack of correlation between pulmonary disease and cystic fibrosis transmembrane conductance regulator dysfunction in cystic fibrosis: a case report

Abstract

IntroductionMutations in both alleles of the cystic fibrosis transmembrane conductance regulator gene result in the disease cystic fibrosis, which usually manifests as chronic sinopulmonary disease, pancreatic insufficiency, elevated sodium chloride loss in sweat, infertility among men due to agenesis of the vas deferens and other symptoms including liver disease.Case presentationWe describe a pair of African-American brothers, aged 21 and 27, with cystic fibrosis. They were homozygous for a rare frameshift mutation in the cystic fibrosis transmembrane conductance regulator 3791delC, which would be expected to cause significant morbidity. Although 80% of cystic fibrosis patients are colonized with Pseudomonas aeruginosa by eight years of age, the older brother had no serum opsonic antibody titer to P. aeruginosa by age 13 and therefore would have failed to mount an effective antibody response to the alginate (mucoid polysaccharide) capsule of P. aeruginosa. He was not colonized with P. aeruginosa until 24 years of age. Similarly, the younger brother was not colonized with P. aeruginosa until age 20 and had no significant lung disease.ConclusionDespite a prevailing idea in cystic fibrosis research that the amount of functional cystic fibrosis transmembrane conductance regulator predicts clinical status, our results indicated that respiratory disease severity in cystic fibrosis exhibits phenotypic heterogeneity. If this heterogeneity is, in part, genetic, it is most likely derived from genes outside the cystic fibrosis transmembrane conductance regulator locus.

Identification of a cystic fibrosis mutation W19X in Tunisia

“…The W19X mutation appears to be severe, since the patient associates infection by Pseudomonas aeruginosa at an early age, while 80% of CF patients are colonized with Pseudomonas aeruginosa by eight years of age [9], dyspnea and severe hypotrophy <4 DS. W19X cystic fibrosis mutation in Tunisia G T T T T T T T T A A A A AA G G G C C C G A 60 70 This nonsense mutation is rare because it has been identified only by Bozon in 1998, in one CF case whose parents are from Tunisia (cystic fibrosis mutation database).…”

Cystic Fibrosis and Infertility

“…It indicates that there is variability in the efficiency of the splicing mechanism both between different individuals and between different organs of the same individual. In many human monogenic diseases, high variability in disease expression is found among patients carrying the same genetic defect (Levy et al, 2010;Rave-Harel et al, 1997). The molecular basis for this variability has been suggested to be allelic heterogeneity, additional genetic loci, and/or environmental factors.…”