The phenotypic consequences of CFTR mutations

Cystic fibrosis is a common autosomal recessive disorder that primarily affects the epithelia] cells in the intestine, I respiratory system, pancreas, gall bladder and sweat glands. Over one thousand mutations have curreutly been identified in the Cystic Fibrosis Transmembrane Conductance Regulator (CF-JR) gene that are associated with CF disease. Therehavebeeri many studies on thecorrelation ofthe CFTRgenotypeand CF disease pheuotype; however, this relationship is still riot well understood. A connection between CFTR genotype and disease inauifested iii the pancreas has been well described, but pulmonary disease appears to be highly variable eveii between individuals -,vith the same enotype. This review describes the current classificatiou of CFTR mutation classes and resultingCF disease phenotypes. Complex disease alleles and modifier genes arc discussed along with alternative disorders, such -is disseminated bronchiectasis and pancreatitis, which arc also thought to result froin CF'I'k mutations.