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Open Access Case report

Challenging the diagnosis of Cystic Fibrosis in a patient carrying the 186-8T/C allelic variant in the CF Transmembrane Conductance Regulator gene

Sara Caldrer12*, Genny Verzè12, Jan Johansson1, Claudio Sorio1, Chiara Angiari2, Mario Buffelli3, Baroukh Maurice Assael2 and Paola Melotti2*

Author Affiliations

1 Department of Pathology and Diagnostics, General Pathology Section, University of Verona School of Medicine, Verona, Italy

2 Cystic Fibrosis Center, Azienda Ospedaliera di Verona, Verona, Italy

3 Department of Neurological Sciences, Physiology Section, University of Verona School of Medicine, Verona, Italy

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BMC Pulmonary Medicine 2014, 14:44  doi:10.1186/1471-2466-14-44

Published: 13 March 2014

Abstract

Background

This report describe for the first time a clinical case with a CFTR allelic variant 186-8T/C (c.54-8 T/C) in intron 1 of CFTR and underline the importance of applying a combination of genetic and functional tests to establish or exclude a diagnosis of Cystic Fibrosis. In this case the diagnostic algorithm proposed for CF has been successfully applied at our Center and previous CF diagnosis assigned in a different Center was not confirmed.

Case presentation

A 38 year-old Italian woman had been treated as affected by CF since 2010, following diagnosis based on sweat tests (reported values of 73 and 57 mEq/L) and a clinical history consistent with CF. No mutations were identified by first level of genetic analysis. Afterwards the patient referred to our center for assessing the relevance of these findings. The genetic variant 186-8T/C (c.54-8 T/C) in intron 1 of the CFTR gene was detected by sequencing. Low-level interstitial-alveolar infiltration was recorded by high-resolution computerized tomography. Lung function was normal and sputum and Broncho Alveolar Lavage cultures resulted bacteriologically negative. Sweat chloride levels was re-assessed and resulted with values of 57 and 35 mEq/L, with a borderline range between 40 and 60 mEq/L. Nasal Potential Difference measurements resulted in three reliable measurements consistent with a non-CF phenotype. Differential diagnosis with ciliary dyskinesia was excluded, as was exon 2 skipping of CFTR gene that might have caused a CFTR functional defect. Furthermore, single cell fluorescence analysis in response to cAMP agonists performed in patient’s monocytes overlapped those obtained in healthy donors.

Conclusion

We concluded that this patient was not affected by CF. This case highlights the need for referrals to highly specialized centers and the importance of combined functional and genetic tests in making a correct diagnosis. Moreover, we confirmed a correlation between NPD tracings and cell depolarization in monocytes providing a rationale for proposing the use of leukocytes as a potential support for CF diagnosis.

Keywords:
Cystic Fibrosis; Cystic Fibrosis Conductance Transmembrane Regulator; Mutation analysis; Nasal potential difference measurements; Cystic fibrosis conductance transmembrane regulator function