title: Cystic fibrosis mutations and genotype-pulmonary phenotype analysis.
abstract: 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.
authors.affiliation: Department of Pediatrics and Biostatistics/Medical Informatics, University of Wisconsin, Madison, WI 53705-2221, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Braun
authors.forename: Philip M
authors.initials: PM
authors.lastname: Farrell
authors.forename: Claude
authors.initials: C
authors.lastname: Ferec
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Audrezet
authors.forename: Anita
authors.initials: A
authors.lastname: Laxova
authors.forename: Zhanhai
authors.initials: Z
authors.lastname: Li
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kosorok
authors.forename: Marjorie A
authors.initials: MA
authors.lastname: Rosenberg
authors.forename: William M
authors.initials: WM
authors.lastname: Gershan
mesh_terms: D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D010641:Phenotype; D017354:Point Mutation; D011379:Prognosis; D011446:Prospective Studies; D013902:Radiography, Thoracic; D012720:Severity of Illness Index; D013147:Spirometry
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA