Cystic fibrosis mutations and genotype-pulmonary phenotype analysis

Andrew T. Braun, Philip M. Farrell, Claude Ferec, Marie Pierre Audrezet, Anita Laxova, Zhanhai Li, Michael R. Kosorok, Marjorie A. Rosenberg, William M. Gershan

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Background: Although there are more than 1000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, most of them are uncommon and only limited information exists regarding genotype-pulmonary phenotype relationships. Methods: We determined and classified the CFTR mutations using denaturing high-performance liquid chromatography and developed new, quantitative methods to categorize pulmonary phenotypes. Results: Two novel alleles were discovered, namely G1047R and 1525-2A → G, which were accompanied by F508del and G551D mutations, respectively. Assessment of numerous options revealed that CF pulmonary phenotype categorization in children cannot be accomplished with clinical or pulmonary function data but is facilitated by longitudinal quantitative chest radiology. It was most useful to categorize pulmonary disease status by evaluating the typical pattern of abnormalities in patients homozygous for the F508del mutation, and then compare patients with minor mutations to this typical CF pulmonary phenotype. By this method, both patients with novel mutations have pulmonary phenotypes typical of F508del homozygotes. However, patients with class IV mutations (e.g., R347P) or with pancreatic sufficiency showed serial chest radiographs that were atypically mild. Conclusions: Longitudinal quantitative chest radiography provides a new strategy for CF pulmonary phenotype categorization that should be useful for genotype-phenotype delineation in individual patients and in both epidemiologic studies and clinical trials involving groups of children with CF.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalJournal of Cystic Fibrosis
Issue number1
StatePublished - Jan 2006

Bibliographical note

Funding Information:
Grant Sponsors: National Institutes of Health (Grant Numbers DK 34108 and M01 RR03186 and M01-RR00058), Cystic Fibrosis Foundation (Grant Number A001-5-010), UW General Clinical Research Center, and Institut National de la Santé et de la Recherche Médicale (INSERM), France.


  • Cystic fibrosis
  • Genotype
  • Lung disease
  • Phenotype


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