Science and Research

Prevalence of meconium ileus marks the severity of mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene

RATIONALE: Meconium ileus (MI) is a perinatal complication in cystic fibrosis (CF), which is only minimally influenced by environmental factors. We derived and examined MI prevalence (MIP) scores to assess CFTR phenotype-phenotype correlation for severe mutations. METHOD: MIP scores were established using a Canadian CF population (n = 2,492) as estimates of the proportion of patients with MI among all patients carrying the same CFTR mutation, focusing on patients with p.F508del as the second allele. Comparisons were made to the registries from the US CF Foundation (n = 43,432), Italy (Veneto/Trentino/Alto Adige regions) (n = 1,788), and Germany (n = 3,596). RESULTS: The prevalence of MI varied among the different registries (13-21%). MI was predominantly prevalent in patients with pancreatic insufficiency carrying "severe" CFTR mutations. In this severe spectrum MIP scores further distinguished between mutation types, for example, G542X (0.31) with a high, F508del (0.22) with a moderate, and G551D (0.08) with a low MIP score. Higher MIP scores were associated with more severe clinical phenotypes, such as a lower forced expiratory volume in 1 second (P = 0.01) and body mass index z score (P = 0.04). CONCLUSIONS: MIP scores can be used to rank CFTR mutations according to their clinical severity and provide a means to expand delineation of CF phenotypes.Genet Med 18 4, 333-340.

  • Dupuis, A.; Keenan, K.; Ooi, C. Y.; Dorfman, R.; Sontag, M. K.; Naehrlich, L.; Castellani, C.; Strug, L. J.; Rommens, J. M.; Gonska, T.


  • Adolescent
  • Adult
  • Alleles
  • Canada/epidemiology
  • Child
  • Cystic Fibrosis/*complications/diagnosis/epidemiology/*genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator/*genetics
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Ileus/diagnosis/*epidemiology/*etiology
  • Male
  • *Meconium
  • *Mutation
  • Phenotype
  • Prevalence
  • Registries
  • Respiratory Function Tests
  • Severity of Illness Index
  • Young Adult
Publication details
DOI: 10.1038/gim.2015.79
Journal: Genetics in medicine : official journal of the American College of Medical Genetics
Pages: 333-40 
Number: 4
Work Type: Original
Location: UGMLC
Disease Area: CFBE
Partner / Member: JLU
Access-Number: 26087176
See publication on PubMed

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