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Cystic fibrosis mutations and disease phenotype
  1. C J TAYLOR,
  2. A DALTON,
  3. O PIRZADA
  1. Cystic Fibrosis Centre
  2. Sheffield Children's Hospital
  3. Western Bank, Sheffield S10 2TH, UK

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    Editor,—Most patients with cystic fibrosis (CF) present in the first year of life with respiratory or gastrointestinal symptoms.1 The diagnosis can be confirmed in cases with this traditional phenotype by sweat testing. More recently, our ability to detect CF mutations and measure transepithelial electrical potential has greatly expanded the clinical spectrum.2 However, Chmiel et al, have expressed concern over basing the diagnosis of CF on the presence of two mutant alleles.3 In support of this, they cite an asymptomatic infant in whom the diagnosis of CF was not confirmed, despite a genotype of dF508/R117H. Our experience, however, does not support their argument.

    Since 1989, we have performed postnatal screening for CF in Trent, and we currently screen approximately 60 000 live births a year. Screening is based on a combination of immunoreactive trypsin (IRT) on day six, with subsequent genotyping for a basket of mutations including dF508 and R117H in individuals with raised IRT levels. Three individuals with the genotype dF508/R117H have been identified by this process. They were all asymptomatic and would not have come to medical attention without screening. In all three, there was no evidence of sinopulmonary disease; all were pancreatic sufficient and sweat testing was not indicative of CF (table 1). Polythymidine tract analysis at intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene demonstrated a 7T/9T background predictive of a non-CF phenotype.

    Table 1

    Patient characteristics

    All three subsequently developed respiratory infections with bacteria typical of CF, including Staphylococcus aureus and Haemophilus influenzae. Pseudomonas aeruginosa was isolated from two of the three, and was eradicated by standard antibiotic treatment. All had abnormal chest radiographs at one year, with changes consistent with CF.

    We suggest that a typical CF phenotype cannot be ruled out in individuals with a dF508/R117H genotype, even with a 7T/9T background. These individuals, who will only be identified through screening programmes, require regular follow up with routine cultures from the airway to allow prompt identification and appropriate treatment of respiratory disease, and thus prevent progressive lung damage.

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