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Article: Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas
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TitleMolecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas
 
AuthorsAhmed, N2
Corey, M2
Forstner, G2
Zielenski, J2
Tsui, LC2
Ellis, L2
Tullis, E1
Durie, P2 2
 
Issue Date2003
 
PublisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
 
CitationGut, 2003, v. 52 n. 8, p. 1159-1164 [How to Cite?]
DOI: http://dx.doi.org/10.1136/gut.52.8.1159
 
AbstractBackground and aims: We tested the hypothesis that the actual or predicted consequences of mutations in the cystic fibrosis transmembrane regulator gene correlate with the pancreatic phenotype and with measures of quantitative exocrine pancreatic function. Methods: We assessed 742 patients with cystic fibrosis for whom genotype and clinical data were available. At diagnosis, 610 were pancreatic insufficient, 110 were pancreatic sufficient, and 22 pancreatic sufficient patients progressed to pancreatic insufficiency after diagnosis. Results: We identified mutations on both alleles in 633 patients (85.3%), on one allele in 95 (12.8%), and on neither allele in 14 (1.9%). Seventy six different mutations were identified. The most common mutation was ΔF508 (71.3%) followed by G551D (2.9%), G542X (2.3%), 621+1G→T (1.2%), and W1282X (1.2%). Patients were categorized into five classes according to the predicted functional consequences of each mutation. Over 95% of patients with severe class I, II, and III mutations were pancreatic insufficient or progressed to pancreatic insufficiency. In contrast, patients with mild class IV and V mutations were consistently pancreatic sufficient. In all but four cases each genotype correlated exclusively with the pancreatic phenotype. Quantitative data of acinar and ductular secretion were available in 93 patients. Patients with mutations belonging to classes I, II, and III had greatly reduced acinar and ductular function compared with those with class IV or V mutations. Conclusion: The predicted or known functional consequences of specific mutant alleles correlate with the severity of pancreatic disease in cystic fibrosis.
 
ISSN0017-5749
2012 Impact Factor: 10.732
2012 SCImago Journal Rankings: 3.379
 
DOIhttp://dx.doi.org/10.1136/gut.52.8.1159
 
PubMed Central IDPMC1773762
 
ISI Accession Number IDWOS:000184182300016
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorAhmed, N
 
dc.contributor.authorCorey, M
 
dc.contributor.authorForstner, G
 
dc.contributor.authorZielenski, J
 
dc.contributor.authorTsui, LC
 
dc.contributor.authorEllis, L
 
dc.contributor.authorTullis, E
 
dc.contributor.authorDurie, P
 
dc.date.accessioned2007-01-29T08:52:24Z
 
dc.date.available2007-01-29T08:52:24Z
 
dc.date.issued2003
 
dc.description.abstractBackground and aims: We tested the hypothesis that the actual or predicted consequences of mutations in the cystic fibrosis transmembrane regulator gene correlate with the pancreatic phenotype and with measures of quantitative exocrine pancreatic function. Methods: We assessed 742 patients with cystic fibrosis for whom genotype and clinical data were available. At diagnosis, 610 were pancreatic insufficient, 110 were pancreatic sufficient, and 22 pancreatic sufficient patients progressed to pancreatic insufficiency after diagnosis. Results: We identified mutations on both alleles in 633 patients (85.3%), on one allele in 95 (12.8%), and on neither allele in 14 (1.9%). Seventy six different mutations were identified. The most common mutation was ΔF508 (71.3%) followed by G551D (2.9%), G542X (2.3%), 621+1G→T (1.2%), and W1282X (1.2%). Patients were categorized into five classes according to the predicted functional consequences of each mutation. Over 95% of patients with severe class I, II, and III mutations were pancreatic insufficient or progressed to pancreatic insufficiency. In contrast, patients with mild class IV and V mutations were consistently pancreatic sufficient. In all but four cases each genotype correlated exclusively with the pancreatic phenotype. Quantitative data of acinar and ductular secretion were available in 93 patients. Patients with mutations belonging to classes I, II, and III had greatly reduced acinar and ductular function compared with those with class IV or V mutations. Conclusion: The predicted or known functional consequences of specific mutant alleles correlate with the severity of pancreatic disease in cystic fibrosis.
 
dc.description.naturepublished_or_final_version
 
dc.format.extent103157 bytes
 
dc.format.extent30208 bytes
 
dc.format.mimetypeapplication/pdf
 
dc.format.mimetypeapplication/msword
 
dc.identifier.citationGut, 2003, v. 52 n. 8, p. 1159-1164 [How to Cite?]
DOI: http://dx.doi.org/10.1136/gut.52.8.1159
 
dc.identifier.doihttp://dx.doi.org/10.1136/gut.52.8.1159
 
dc.identifier.epage1164
 
dc.identifier.isiWOS:000184182300016
 
dc.identifier.issn0017-5749
2012 Impact Factor: 10.732
2012 SCImago Journal Rankings: 3.379
 
dc.identifier.issue8
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC1773762
 
dc.identifier.pmid12865275
 
dc.identifier.scopuseid_2-s2.0-0038298386
 
dc.identifier.spage1159
 
dc.identifier.urihttp://hdl.handle.net/10722/42535
 
dc.identifier.volume52
 
dc.languageeng
 
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofGut
 
dc.relation.referencesReferences in Scopus
 
dc.rightsGut. Copyright © B M J Publishing Group.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshCystic fibrosis
 
dc.subject.meshCystic fibrosis transmembrane regulator
 
dc.subject.meshPancreatic insufficiency
 
dc.subject.meshPancreas
 
dc.subject.meshExocrine pancreatic insufficiency - genetics - physiopathology
 
dc.titleMolecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas
 
dc.typeArticle
 
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Author Affiliations
  1. Saint Michael's Hospital University of Toronto
  2. Hospital for Sick Children University of Toronto