Document Detail

Correlation between genotype and phenotype in patients with cystic fibrosis. The Cystic Fibrosis Genotype-Phenotype Consortium.
MedLine Citation:
PMID:  8166795     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Cystic fibrosis is the most common lethal autosomal recessive disorder among whites. Seventy-two percent of patients with this disease are homozygotes or compound heterozygotes for eight mutations of the cystic fibrosis transmembrane conductance regulator gene on chromosome 7: delta F508, G542X, R553X, W1282X, N1303K, 621 + 1G-->T, 1717-1G-->A, and R117H. We studied the relation between genotype and phenotype in patients from 14 countries. METHODS: Each of 399 patients who were compound heterozygotes for delta F508 and one other mutation was matched with the delta F508 homozygote of the same sex who was the closest in age from the same center. A paired analysis was performed of the following outcome variables: age at diagnosis, sweat chloride concentration, growth percentiles, pulmonary-function values, chest-film score, pseudomonas colonization, nasal polyps, pancreatic sufficiency, pancreatitis, diabetes mellitus, meconium ileus, distal intestinal obstruction syndrome, rectal prolapse, cirrhosis, and gallbladder disease. RESULTS: The compound heterozygotes having the genotype R117H/delta F508 clearly differed from the age- and sex-matched delta F508 homozygotes: they more often had pancreatic sufficiency (87 percent vs. 4 percent, P < 0.001), were older when the diagnosis was first made (mean [+/- SD] age, 10.2 +/- 10.5 vs. 2.5 +/- 4.3 years; P = 0.002), and had lower sweat chloride concentrations (80 +/- 18 vs. 108 +/- 14 mmol per liter, P < 0.001). There were no statistically significant differences between delta F508 homozygotes and other compound heterozygotes with regard to any variable tested. CONCLUSIONS: Prenatal and prognostic counseling for patients with the R117H/delta F508 genotype should include the likelihood that they will have long-term pancreatic sufficiency. Patients with the other genotypes should expect the early onset of pancreatic insufficiency. For none of the genotypes studied can predictions be made about the occurrence of common complications or the severity or course of pulmonary disease.
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The New England journal of medicine     Volume:  329     ISSN:  0028-4793     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  1993 Oct 
Date Detail:
Created Date:  1993-11-01     Completed Date:  1993-11-01     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1308-13     Citation Subset:  AIM; IM    
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MeSH Terms
Chromosomes, Human, Pair 7
Cross-Sectional Studies
Cystic Fibrosis / genetics*
Grant Support
Comment In:
N Engl J Med. 1994 Mar 24;330(12):865-6; author reply 866-7   [PMID:  8114850 ]
N Engl J Med. 1994 Mar 24;330(12):866   [PMID:  8114851 ]

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