Phenotypic and genetic characterization of patients with features of "nonclassic" forms of cystic fibrosis.
OBJECTIVE
To determine which features of incomplete or "nonclassic" forms of cystic fibrosis (CF) are associated with deleterious CF transmembrane conductance regulator gene ( CFTR ) mutations, and to explore other etiologies for features not associated with deleterious CFTR mutations.


METHODS
Clinical features were compared between 57 patients with deleterious mutations in each CFTR and 63 with no deleterious mutations. The Shwachman Bodian Diamond syndrome gene ( SBDS ) was sequenced to search for mutations in patients with no deleterious CFTR mutations and steatorrhea to determine if any had unrecognized Shwachman-Diamond syndrome (SDS).


RESULTS
The presence of a common CF-causing mutation, absence of the vas deferens, and Pseudomona aeruginosa in the sputum correlated with the presence of two deleterious CFTR mutations, whereas sweat chloride concentration, diagnostic criteria for CF, and steatorrhea did not. However, sweat chloride concentration correlated with CFTR mutation status in patients infected with P aeruginosa. One patient had disease-causing mutations in each SBDS .


CONCLUSIONS
Presence of a common CF-causing mutation, absence of the vas deferens and/or P aeruginosa infection in a patient with features of nonclassic CF are predictive of deleterious mutations in each CFTR , whereas steatorrhea in the same context is likely to have etiologies other than CF transmembrane conductance regulator (CFTR) dysfunction.
Groman
Joshua D
JD
Cyctic Fibrosis Foundation Genotyping Center and McKusick-Nathans Institute of Genetic Medicine, Bloomberg School of Public Health, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21287, USA.
Karczeski
Barbara
B
Sheridan
Molly
M
Robinson
Terry E
TE
Fallin
M Daniele
MD
Cutting
Garry R
GR
D000328:Adult; D002648:Child; D003550:Cystic Fibrosis / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D045602:Steatorrhea / Q000235:genetics
C505032:CFTR protein, human; D011506:Proteins; C470521:SBDS protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator