title: Cystic fibrosis: the impact of analytical technology for genotype-phenotype studies.
abstract: The generalized exocrinopathy cystic fibrosis (CF) is the most common severe genetic disease in Caucasian populations. A panel of more than 700 chromosomes from German and Turkish CF patients was screened for disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene by chemical cleavage of mismatch, single strand conformation polymorphism, restriction analysis and direct sequencing of genomic DNA amplified by polymerase chain reaction. Besides the major 3-bp deletion, delta F508 that was found on 73% of German CF chromosomes, more than 50 other missense, nonsense, frame-shift, and splice-site mutations have already been identified. In general, a CFTR mutation is linked with a single 10-marker haplotype which indicates that in most cases a particular mutation spread from a common ancestor. The comparison of mutation genotypes with the disease phenotype emphasized the causative role of the type and localization of the CFTR mutation for clinical course and prognosis. Pancreatic status and the risk of colonization of airways with opportunistic pathogens are genetically determined. Most patients who are harbouring mutations in the nucleotide binding folds were suffering from severe CF disease. Mild or even aberrant forms of CF were observed for many missense mutations located in the putative transmembrane domains or for mutations that are expected to result in a truncated protein of half of wild-type CFTR.
authors.affiliation: Klinische Forschergruppe Molekulare Pathologie der Mukoviszidose, Abteilung Biophysikalische Chemie, Medizinische Hochschule Hannover, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Tümmler
authors.forename: T
authors.initials: T
authors.lastname: Dörk
authors.forename: P
authors.initials: P
authors.lastname: Kubesch
authors.forename: R
authors.initials: R
authors.lastname: Fislage
authors.forename: N
authors.initials: N
authors.lastname: Kälin
authors.forename: T
authors.initials: T
authors.lastname: Neumann
authors.forename: U
authors.initials: U
authors.lastname: Wulbrand
authors.forename: B
authors.initials: B
authors.lastname: Wulf
authors.forename: G
authors.initials: G
authors.lastname: Steinkamp
authors.forename: H
authors.initials: H
authors.lastname: von der Hardt
mesh_terms: D003550:Cystic Fibrosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D010641:Phenotype