Variant Cystic Fibrosis Phenotypes in the Absence of CFTR Mutations

Classic cystic fibrosis is an autosomal recessive disorder that is caused by loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene. Clinical manifestations in the airways, pancreas, male reproductive tract, and sweat glands that resemble those occurring in classic cystic fibrosis have been observed in patients with mutations that reduce, but do not eliminate, the function of CFTR protein. This study included 30 patients who had no identifiable CFTR mutations and who had some features of cystic fibrosis but did not meet a clinical definition of classic cystic fibrosis. The authors conclude that this variant phenotype derives from factors other than mutations in the CFTR gene. Cystic fibrosis has been recognized as a distinct clinical entity for more than 60 years. 1 The observation that affected patients have excessive salt loss 2 was a major milestone in the diagnosis of cystic fibrosis, leading to the development of the sweat test. 3 The advent of this biochemical test facilitated the diagnosis in patients with a wide range of phenotypes, including older children and adults who had evidence of clinical disease in only a subgroup of the organ systems involved in classic cystic fibrosis. These forms are termed “nonclassic cystic fibrosis” and account for at least 10 percent of cases. 4 – . . .