Cystic fibrosis with three mutations in the cystic fibrosis transmembrane conductance regulator gene.

摘要: Three mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene were discovered a pancreas-insufficient patient with (CF) who displayed an uncommon combination of almost normal chloride concentration sweat tests and typical symptoms gastrointestinal pulmonary disease. The R553Q mutation was found on maternal ΔF508-CFTR gene. Codon 553 is located within consensus motif ATP-binding cassette transport proteins at less conserved position. Other members this protein superfamily contain glutamine instead arginine homologous position, suggesting modulating rather than disease-causing role CFTR. amplification refractory system did not detect further 65 normal, 113 ΔF508, 91 non-ΔF508 CF chromosomes. index case carried R553X nonsense paternal chromosome. present 9 out 86 German nonΔF508 chromosomes linked XV2c-KM19Mp6d9-J44-GATT haplotypes 2-2-2-1-1 1-1-2-1-2. location separate including both alleles intragenic GATT repeat suggests ancient and/or multiple origins mutations. association genotype CFTR clinical phenotype assessed for patients carrying related genotypes ΔF508/ΔF508 (n = 80), ΔF508/R553X 9) ΔF508-R553Q/R553X 1). In compound heterozygotes, median pilocarpine iontophoresis significantly lower ΔF508 homozygotes (P < 0.01). groups different respect to distributions centiles height 0.001) weight 0.01) as most sensitive predictors course prognosis CF. Growth retardation more pronounced heterozygotes.