Cystic fibrosis: recent advances in genetics and molecular biology

Cystic fibrosis (CF) is the most common lethal hereditary disease of Caucasians, occurring once for every 2,000 live births. One out of 20 persons in the United States white population is a heterozygous carrier. An autosomal recessive pattern of inheritance is well established. The disease affects the respiratory and digestive tracts most severely. Despite the clearcut hereditary nature of the disease, insight into the biochemistry of CF has been almost totally lacking until very recently. New evidence strongly indicates that abnormal chloride ion transportation underlies the clinical manifestations. Recent advances in molecular genetics have established that the CF disease gene is located on the long arm of chromosome 7. Several restriction fragment length polymorphisms (RFLP) markers are closely linked to the CF gene. These markers permit antenatal testing of samples from fetuses at risk for CF with a high probability of disease prediction. One laboratory has isolated a desoxyribonucleic acid (DNA) sequence from chromosome 7 which is a candidate for the CF gene itself. A protein called the CF antigen is coded by a gene on chromosome 1. Patients with CF and carriers have abnormally high serum levels of this protein. In the normal state, the product of the CF gene on chromosome 7 may interact with the product of the gene on chromosome 1, enabling its normal catabolism and function. The structure of the CF antigen suggests that it may regulate ion transport.