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Rapid characterization of the variable length polythymidine tract in the cystic fibrosis (CFTR) gene: association of the 5T allele with selected CFTR mutations and its incidence in atypical sinopulmonary disease.
Friedman, K J; Heim, R A; Knowles, M R; Silverman, L M.
Affiliation
  • Friedman KJ; University of North Carolina, Chapel Hill 27154, USA. bluemold@med.unc.edu
Hum Mutat ; 10(2): 108-15, 1997.
Article in En | MEDLINE | ID: mdl-9259194
ABSTRACT
The CFTR intron 8 variable length polythymidine tract modulates the cystic fibrosis (CF) phenotype associated with the mutation R117H. To explore whether other mutations reside on multiple intron 8 backgrounds with discernible impacts on phenotype, we developed an allele-specific PCR assay to characterize this locus. Our approach types samples rapidly without the use or radioisotopes. Polythymidine alleles were identified for mutations either associated with a wide range of clinical phenotypes (R117H, R347P, G85E, D1152H, R334W, 2789 + 5 G > A, 3849 + 10kb C > T), and/or located at hypermutable CpG loci (R117H, 3845 + 10kb C > T, R553X, R334W, S945L and R75Q). R117H was detected in cis with each of three alleles (5T, 7T, 9T) at the intron 8 locus. The novel R117H-9T association was detected in a 10-month African-American male with borderline-to-mildly elevated sweat chloride values (approximately 50-66 mEq/L). All other mutations studied were associated with 7T except 3849 + 10kb C > T, which was detected on both 7T and 9T backgrounds, but not 5T. Three individuals with a delta F508/3849 + 10kb C > T genotype were 9T,9T and had pancreatic sufficiency and normal sweat chloride values, whereas 15 others who carried 3849 + 10kb C > T on a 7T background had variable pancreatic function (sufficient, n = 12, insufficient, n = 3), and variable sweat chloride values (normal, n = 12, elevated, n = 3). Surprisingly, when not associated with known CFTR mutations, 5T was detected with elevated frequency among individuals with sinopulmonary disease of ill-defined etiology, but with some characteristics of variant CF. In summary, the 5T allele was not found in cis with CF-causing mutations besides R117H, but an elevated 5T allele frequency in variant CF patients suggests 5T may be associated with disease in some situations.
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Collection: 01-internacional Database: MEDLINE Main subject: Repetitive Sequences, Nucleic Acid / Cystic Fibrosis Transmembrane Conductance Regulator / Cystic Fibrosis / Lung Diseases / Mutation Type of study: Incidence_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Language: En Journal: Hum Mutat Journal subject: GENETICA MEDICA Year: 1997 Document type: Article Affiliation country:
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Collection: 01-internacional Database: MEDLINE Main subject: Repetitive Sequences, Nucleic Acid / Cystic Fibrosis Transmembrane Conductance Regulator / Cystic Fibrosis / Lung Diseases / Mutation Type of study: Incidence_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Language: En Journal: Hum Mutat Journal subject: GENETICA MEDICA Year: 1997 Document type: Article Affiliation country:
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