| Autor: |
Marisa Sousa, Maria F Servidoni, Adriana M Vinagre, Anabela S Ramalho, Luciana C Bonadia, Verónica Felício, Maria A Ribeiro, Inna Uliyakina, Fernando A Marson, Arthur Kmit, Silvia R Cardoso, José D Ribeiro, Carmen S Bertuzzo, Lisete Sousa, Karl Kunzelmann, Antônio F Ribeiro, Margarida D Amaral |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 7, Iss 10, p e47708 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0047708 |
| Popis: |
BackgroundCystic Fibrosis (CF) is caused by ∼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 findingsTo 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 (Conclusions/significanceDetermination 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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