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Analysis of the entire coding region of the cystic fibrosis transmembrane regulator gene in neonatal hypertrypsinaemia with normal sweat test
  1. *Cystic Fibrosis Centre, Ospedale Civile Maggiore, Piazzale Stefani 1, 37126 Verona, Italy
  2. †Department of Mother and Child, Biology and Genetics, Section of Biology and Genetics, University of Verona, Verona, Italy
  1. Dr Castellani, carlocastellani{at}

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Editor—Measurement of immunoreactive trypsinogen concentration (IRT) in dried blood spots is the most common technique for neonatal screening for cystic fibrosis (CF).1 Since a considerable number of newborns show raised IRT levels, several laboratories improve the screening specificity by testing infants with hypertrypsinaemia for the most common CF mutations. Diagnosis is established in neonates carrying two mutations, but a sweat test is required if only one mutation is found, in order to detect affected subjects with a second, unrecognised mutation. Infants with raised IRT, one CF mutation, and normal sweat electrolyte concentrations are usually considered to be just carriers.

Unexpectedly, a frequency of CF heterozygotes significantly higher than in the general population has been repeatedly reported among neonates with hypertrypsinaemia and normal sweat chloride levels.2 3 It is not clear whether having one CF mutation, perhaps together with some unknown pathogenetic factor, is sufficient to predispose to neonatal hypertrypsinaemia. Such a hypothesis is corroborated by the findings of Lecoqet al,4 who showed that the probability of a newborn being a carrier of the majorCFTR mutation, ΔF508, increases with neonatal IRT concentration, and suggested that heterozygotes may have early subclinical impairment of exocrine pancreatic function. Alternatively, it could be speculated that at least some hypertrypsinaemic newborns who, after testing for a limited number of CF mutations have been found to carry a CFTRgene mutation, have on the other chromosome an undetected mild mutation, and possibly suffer from an atypical form of CF, characterised by a negative sweat test. A DNA polymorphic sequence of five thymines in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is very commonly involved in the pathogenesis of a primarily genital form of CF called congenital bilateral absence of the vas deferens (CBAVD),5 …

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