Cystic fibrosis (CF) is the most common autosomal recessive disease within the Caucasian population, exhibiting an incidence of 1 in 2500 births. The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene, causing CF when both chromosomal copies are impaired, was identified in 1989. The CF causing gene is known for the phenomenon called allelic heterogeneity: More than 1000 variants of CFTR have been described.
The symptoms of CF are caused by an impaired function of exocrine glands in many CFTR expressing organs, predominantly within the gastrointestinal and respiratory tracts. Major manifestations of the disease are a consequence of chronic obstruction: bronchitis and bronchiectasis (obstruction of the airways) combined with chronic infection by bacterial pathogens such as Pseudomonas aeruginosa, pancreatic insufficiency (obstruction of the pancreatic duct), meconium ileus (obstruction of the intestine), biliary cirrhosis (obstruction of the biliary duct) and reduced fertility or infertility in both genders (obstruction within the reproductive organs).
Analysis of CFTR Function and Expression
In vitro and ex vivo characterisation of mutant CFTR phenotypes and CFTR expression in non-CF disease: The most frequent CF disease causing lesion, F508del, was characterised as a protein processing mutant. However, in patient's tissues, correct expression and residual function of F508del-CFTR was observed...MORE
The European Cystic Fibrosis Twin and Sibling Study
In 1995, an initiative of the CF research groups from Rotterdam and Hannover launched the European CF Twin and Sibling Study to uncover why the manifestation of CF is so variable even though this is the textbook example of a monogenic disease...MORE
CF Modifying Genes
The variability of CF disease severity can be attributed to the CFTR genotype, epigenetic factors and disease modulating genes. The "European Cystic Fibrosis Twin and Sibling Study" pursues a classical approach of quantitative human genetics to identify modifying genes that determine the cystic fibrosis phenotype...MORE
Cystic fibrosis mouse models
Actually, we are using two mouse models for Cystic Fibrosis for our research targets. The first was established in 1992 by Dorin et al. by targeted mutation using an insertional gene targeting vector to disrupt exon 10 of the murine Cftr gene in 129P2 embryonic stem cells...MORE
Atypical Cystic Fibrosis, Rare CFTR Mutations and Unusual CF Phenotypes
Most cystic fibrosis patients are diagnosed based on elevated sweat chloride, two mutations within the CFTR gene and CF typical symptoms. Some cases do not fit into that picture...MORE
The CFTR genomic region was visualized as avilable by 07-2014 from http://genome.ucsc.edu; Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. The human genome browser at UCSC. Genome Res. 2002 Jun;12(6):996-1006