title: Prevalence of meconium ileus marks the severity of mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Clinical Research Services, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.|Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Annie
authors.identifier: http://orcid.org/0000-0002-8704-078X
authors.initials: A
authors.lastname: Dupuis
authors.affiliation: Program in Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Katherine
authors.initials: K
authors.lastname: Keenan
authors.affiliation: Discipline of Paediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.|Department of Gastroenterology, Sydney Children's Hospital Randwick, New South Wales, Australia.
authors.forename: Chee Y
authors.identifier: http://orcid.org/0000-0001-7111-0926
authors.initials: CY
authors.lastname: Ooi
authors.affiliation: GeneYouIn Inc., Toronto, Ontario, Canada.
authors.forename: Ruslan
authors.identifier: http://orcid.org/0000-0002-3421-5582
authors.initials: R
authors.lastname: Dorfman
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Marci K
authors.identifier: http://orcid.org/0000-0003-2501-652X
authors.initials: MK
authors.lastname: Sontag
authors.affiliation: Department of Pediatrics, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Naehrlich
authors.affiliation: Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Castellani
authors.affiliation: Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.|Program in Genetics & Genome Biology, Research Institute, The Hospital for Sick Children and Division of Biostatistics.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Strug
authors.affiliation: Program in Genetics & Genome Biology, Research Institute, The Hospital for Sick Children and Division of Biostatistics.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Johanna M
authors.identifier: http://orcid.org/0000-0001-8732-825X
authors.initials: JM
authors.lastname: Rommens
authors.affiliation: Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.|Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tanja
authors.identifier: http://orcid.org/0000-0001-6786-4354
authors.initials: T
authors.lastname: Gonska
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002170:Canada / Q000453:epidemiology; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D045823:Ileus / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D008470:Meconium; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D012042:Registries; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator