Dokumentenart: | Artikel | ||||
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Titel eines Journals oder einer Zeitschrift: | PLoS ONE | ||||
Verlag: | PUBLIC LIBRARY SCIENCE | ||||
Ort der Veröffentlichung: | SAN FRANCISCO | ||||
Band: | 7 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 10 | ||||
Seitenbereich: | e47708 | ||||
Datum: | 2012 | ||||
Institutionen: | Biologie und Vorklinische Medizin > Institut für Physiologie > Prof. Dr. Karl Kunzelmann | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | TRANSMEMBRANE CONDUCTANCE REGULATOR; NASAL POTENTIAL DIFFERENCE; AIRWAY ION-TRANSPORT; PULMONARY-DISEASE; LUNG-FUNCTION; MUTATION; IDENTIFICATION; CONSENSUS; GENOTYPE; GENE; | ||||
Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 63269 |
Zusammenfassung
Background: Cystic Fibrosis (CF) is caused by similar to 1,900 mutations in the CF transmembrane conductance regulator (CFTR) gene encoding for a cAMP-regulated chloride (Cl-) channel expressed in several epithelia. Clinical features are dominated by respiratory symptoms, but there is variable organ involvement thus causing diagnostic dilemmas, especially for non-classic cases. ...
Zusammenfassung
Background: Cystic Fibrosis (CF) is caused by similar to 1,900 mutations in the CF transmembrane conductance regulator (CFTR) gene encoding for a cAMP-regulated chloride (Cl-) channel expressed in several epithelia. Clinical features are dominated by respiratory symptoms, but there is variable organ involvement thus causing diagnostic dilemmas, especially for non-classic cases. Methodology/Principal Findings: To further establish measurement of CFTR function as a sensitive and robust biomarker for diagnosis and prognosis of CF, we herein assessed cholinergic and cAMP-CFTR-mediated Cl- secretion in 524 freshly excised rectal biopsies from 118 individuals, including patients with confirmed CF clinical diagnosis (n = 51), individuals with clinical CF suspicion (n = 49) and age-matched non-CF controls (n = 18). Conclusive measurements were obtained for 96% of cases. Patients with "Classic CF'', presenting earlier onset of symptoms, pancreatic insufficiency, severe lung disease and low Shwachman-Kulczycki scores were found to lack CFTR-mediated Cl- secretion (<5%). Individuals with milder CF disease presented residual CFTR-mediated Cl- secretion (10-57%) and non-CF controls show CFTR-mediated Cl- secretion >= 30-35% and data evidenced good correlations with various clinical parameters. Finally, comparison of these values with those in "CF suspicion'' individuals allowed to confirm CF in 16/49 individuals (33%) and exclude it in 28/49 (57%). Statistical discriminant analyses showed that colonic measurements of CFTR-mediated Cl- secretion are the best discriminator among Classic/Non-Classic CF and non-CF groups. Conclusions/Significance: Determination of CFTR-mediated Cl- secretion in rectal biopsies is demonstrated here to be a sensitive, reproducible and robust predictive biomarker for the diagnosis and prognosis of CF. The method also has very high potential for (pre-) clinical trials of CFTR-modulator therapies.
Metadaten zuletzt geändert: 19 Dez 2024 09:34