Diagnosis of Cystic Fibrosis — Detection of the Gene Deletion Delta F 508

Abstract

Cystic fibrosis (CF) is an autosomal recessive disorder with an average incidence of 1:2500 in Caucasians. In CF, increased viscosity of exocrine secretions, caused by disturbed permeability of the cellular membrane for chloride ions, leads to gastrointestinal and bronchopulmonary obstruction followed by malabsorption, pneumonia and bronchiectasia. The locus of a putative CF gene could be assigned to chromosome 7q31 and molecular genetic analyses were established with DNA probes for polymorphic markers linked to the CF locus based on RFLP. Studies within CF families and prenatal diagnosis were thus made possible, if an index patient’s haplotype was known [2]. RFLP studies with linked polymorphic DNA markers, however, were not suitable for clinical diagnosis which had to rely on clinical symptoms and nonspecific laboratory tests. Identification and cloning of the CF gene [13, 14] and the discovery of the deletion Delta F 508 [9] provided a new dimension in diagnosis of CF. Found in 68% of CF chromosomes and predominantly associated with a certain haplotype, Delta F 508 seemed to represent the most important mutation involved in CF. It is to a great extent found in CF patients with insufficient pancreatic function. Delta F 508 causes the loss of phenylalanine in a supposed CF transmembrane regulation protein, which affects a prospective ATP-binding site and thus a regular transport of chloride ions [13].