JOURNAL OF MEDICAL CASE REPORTS Levy et al. Journal of Medical Case Reports 2010, 4:117 http://www.jmedicalcasereports.com/content/4/1/117 Open Access CASE REPORT BioMed Central © 2010 Levy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons At- tribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Case report Lack of correlation between pulmonary disease and cystic fibrosis transmembrane conductance regulator dysfunction in cystic fibrosis: a case report Hara Levy* 1,2,3 , Carolynn L Cannon 4 , Daniel Asher 1 , Christopher García 3 , Robert H Cleveland 2,5 , Gerald B Pier 2,3 , Michael R Knowles 6 and Andrew A Colin 7 Abstract Introduction: Mutations 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 presentation: We 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. Conclusion: Despite 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. Introduction Mutations in both alleles of the cystic fibrosis transmem- brane conductance regulator (CFTR) gene result in the disease cystic fibrosis (CF), which manifests classically as chronic sinopulmonary disease, pancreatic insufficiency, elevated sodium chloride loss in sweat, infertility among men is due to agenesis of the vas deferens and other symptoms like liver disease. Except for patients with sig- nificant liver disease, the primary disease morbidity is linked to the chronic pulmonary infections and conse- quent decline in lung function. CFTR mutations are clas- sified as severe (class I-III mutations) or mild (class IV-V mutations) based on their effect on protein synthesis and function, implying that the less CFTR that is made or is functional, the more severe the clinical course of a patient with cystic fibrosis (CF) [1-4]. Importantly, none of the CFTR mutations correlate with sweat chloride levels and only few of the more than 1,500 identified mutations in CFTR result in an expected respiratory disease pheno- type in homozygous or compound heterozygous patients. It is well-accepted that the diversity of lung disease among CF patients is not accounted for either by varia- tion in CFTR mutations or by level of sweat chloride as there is considerable phenotypic heterogeneity even in patients with the same class of CFTR mutation. In this report, we describe a pair of siblings with a mild CF phe- notype, who are homozygous for the 3791delC mutation, * Correspondence: hlevy@mcw.edu 1 Division of Pulmonary Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, USA Full list of author information is available at the end of the article