Silke Hedtfeld

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BACKGROUND The cystic fibrosis (CF) basic defect, caused by dysfunction of the apical chloride channel CFTR in the gastrointestinal and respiratory tract epithelia, has not been employed so far to support the role of CF modifier genes. METHODS Patients were selected from 101 families with a total of 171 F508del-CFTR homozygous CF patients to identify CF(More)
BACKGROUND The basic defect of the autosomal recessive disorder cystic fibrosis (CF) manifests in chloride hyposecretion and sodium hyperabsorption. CF-like disease has been reported in a heterozygous carrier of F508del CFTR and the hyperactive variant p.W493R-SCNN1A of the epithelial sodium channel (ENaC). METHODS The hypothesis that heterozygosity for(More)
We have used a stepwise approach consisting of initial interrogation, confirmation and fine mapping to analyze STAT3, IL1B and IFNGR1 as modifiers of cystic fibrosis disease building upon the data and sample collection of the European Cystic Fibrosis Twin and Sibling Study. We have observed direct correlation between the length of the intronic(More)
BACKGROUND F508del-CFTR, the most frequent disease-causing mutation among Caucasian cystic fibrosis (CF) patients, has been characterised as a mutant defective in protein folding, processing and trafficking. We have investigated the two neighbouring cytokeratin genes KRT8 and KRT18 in a candidate gene approach to ask whether variants in KRT8 and/or KRT18(More)
The three-base-pair deletion c.1521_1523delCTT (p.Phe508del, F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) is the most frequent disease-causing lesion in cystic fibrosis (CF). The CFTR gene encodes a chloride and bicarbonate channel at the apical membrane of epithelial cells. Altered ion transport of CFTR-expressing epithelia(More)
Pseudomonas aeruginosa is the major pathogen in chronic lung infections of individuals with cystic fibrosis (CF). Unrelated CF patients may acquire P. aeruginosa from the environment or by cross-infection in the CF setting. We tested the efficacy of measures to prevent nosocomial acquisition of P. aeruginosa at a Paediatric CF centre in a prospective(More)
On 19q13, TGFB1 and the cystic fibrosis modifier 1 locus (CFM1) have been identified as modifiers of the course of the monogenic disease cystic fibrosis (CF). Recently, we have described a transmission disequilibrium at the microsatellite D19S197, localized between TGFB1 and CFM1. To map the corresponding molecular variants, we have selected informative SNP(More)
The manifestation of the monogenic disease cystic fibrosis results from the cystic fibrosis transmembrane conductance regulator (CFTR)-mediated basic defect defined as an altered chloride transport. An association study using contrasting endophenotypes was conducted with 17 markers to allow fine-mapping of a previously reported association signal within the(More)
Chronic airway infections determine most morbidity in people with cystic fibrosis (CF). Herein, we present unbiased quantitative data about the frequency and abundance of DNA viruses, archaea, bacteria, moulds and fungi in CF lower airways. Induced sputa were collected on several occasions from children, adolescents and adults with CF. Deep sputum(More)
Cystic fibrosis (CF) is a monogenic disease characterized by a high variability of disease severity and outcome that points to the role of environmental factors and modulating genes that shape the course of this multiorgan disease. We genotyped families of cystic fibrosis sib pairs homozygous for F508del-CFTR who represent extreme clinical phenotypes at(More)