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Editor-in-chief
Maria Stella Graziani

Deputy Director
Martina Zaninotto

Associate Editors
Ferruccio Ceriotti
Davide Giavarina
Bruna Lo Sasso
Giampaolo Merlini
Martina Montagnana
Andrea Mosca
Paola Pezzati
Rossella Tomaiuolo
Matteo Vidali

EIC Assistant
Francesco Busardò

International Advisory Board Khosrow Adeli Canada
Sergio Bernardini Italy
Marcello Ciaccio Italy
Eleftherios Diamandis Canada
Philippe Gillery France
Kjell Grankvist Sweden
Hans Jacobs The Netherlands
Eric Kilpatrick UK
Magdalena Krintus Poland
Giuseppe Lippi Italy
Mario Plebani Italy
Sverre Sandberg Norway
Ana-Maria Simundic Croatia
Tommaso Trenti Italy
Cas Weykamp The Netherlands
Maria Willrich USA
Paul Yip Canada

Publisher
Biomedia srl
Via L. Temolo 4, 20126 Milano

Responsible Editor
Giuseppe Agosta

Editorial Secretary
Chiara Riva
Biomedia srl
Via L. Temolo 4, 20126 Milano
Tel. 0245498282
email: biochimica.clinica@sibioc.it

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ISSN print: 0393 – 0564
ISSN digital: 0392- 7091

BC: Articoli scritti da F. Amato

Identificazione e caratterizzazione di mutazioni in regioni regolatorie del gene malattia della fibrosi cistica
Identification and characterization of mutations in regulatory regions of cystic fibrosis disease gene
M. Scorza \| A. Elce \| S. Giordano \| F. Amato \| B. Lo Sasso \| F. Zarrilli \| R. Tomaiuolo \|
<p>Mutation epidemiology is crucial for cystic fibrosis (CF) diagnosis and counselling. ~6%-7% of alleles from CF patients do not bear mutations in the coding regions of the Cystic Fibrosis Transmembrane Regulator (CFTR) disease gene. In these patients, mutations may be present in non-coding, regulatory regions of the gene as i) intronic regions (particularly in high conserved sequences), ii) the promoter region or iii) the area at the 3’ of the gene, which is the target of microRNA regulation. We studied these regions by gene sequencing in a group of CF patients with one or both unidentified mutations after the analysis of CFTR coding regions, and in a group of CF patients with a different clinical expression of disease to evaluate if mutations in such regions may have a role in modulating CF clinical expression. Our analysis revealed: i) a dozen of mutations (most novel) in the large promoter area of 6000 bp at the 5’ of the gene; expression studies in four cell lines demonstrated that a half of such mutations may have a pathogenic effect; ii) a series of mutations in 52 conserved sequence tags (CSTs), i.e. intronic regions with a high homology between humans and mouse; expression studies revealed the pathogenic effect of one of these mutations; iii) finally, three mutations in the 1500 bp region at the 3’ of the gene; one of this has a pathogenic role, enhancing the interaction of CFTR with two inhibitory microRNAs. To the best of our knowledge, this is the first example of such pathogenic mechanism in a monogenic disorder. On the contrary, no mutations were identified in patients with different clinical expression in any of the three<br />non-coding regions. To conclude, the sequencing of non coding regions may improve the detection rate of molecular analysis in CF, but functional studies are required to define the pathogenic effect of novel mutations.</p>
Biochimica Clinica ; 37(6) 465-469 Contributi scientifici - Scientific papers