[Cystic fibrosis. From clinical diagnosis to a mutation specific test]

By use of classical linkage analysis and modern DNA technology the gene for cystic fibrosis (CF) was mapped to the long arm of chromosome 7 in 1985. Cloning of the entire gene (CFTR = Cystic Fibrosis Transmembrane Conductance Regulator) was published in 1989. The most common mutation (delta F508) is a three base pair deletion in exon 10, which results in a protein without the amino acid phenylalanine at position 508. The frequency of this mutation varies among different populations, ranging from 45% in the Mediterranean countries to a height in Denmark of 88% of the disease genes. More than 150 different mutations have been identified so far, most of which are very rare. CF is one of the most common severe inherited diseases, but the cloning of the gene and identification of the mutations give great possibilities for prevention permitting both carrier and prenatal diagnosis. The function of the CFTR protein is still not fully known. However, the amino acid sequence of the protein is highly homologous to those of several membrane proteins. In vitro transfection experiments indicate that it constitutes a chloride channel. Recently in vivo experiments involving somatic gene therapy on rats have been successful.