{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:52:11Z","timestamp":1790376731137,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T00:00:00Z","timestamp":1429056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Vaincre La Mucoviscidose (VLM)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Respiratory J"],"published-print":{"date-parts":[[2016,11]]},"abstract":"Abstract<\/jats:title>Background and Aims<\/jats:title>P<\/jats:italic><\/jats:styled-content>seudomonas aeruginosa<\/jats:italic> (Pa<\/jats:styled-content>) infection in cystic fibrosis (CF<\/jats:styled-content>) patients is associated with worse long\u2010term pulmonary disease and shorter survival, and chronic Pa<\/jats:styled-content> infection (CPA<\/jats:styled-content>) is associated with reduced lung function, faster rate of lung decline, increased rates of exacerbations and shorter survival. By using exome sequencing and extreme phenotype design, it was recently shown that isoforms of dynactin 4 (DCTN<\/jats:styled-content>4) may influence Pa<\/jats:styled-content> infection in CF<\/jats:styled-content>, leading to worse respiratory disease. The purpose of this study was to investigate the role of DCTN<\/jats:italic><\/jats:styled-content>4<\/jats:italic> missense variants on Pa<\/jats:styled-content> infection incidence, age at first Pa<\/jats:styled-content> infection and chronic Pa<\/jats:styled-content> infection incidence in a cohort of adult CF<\/jats:styled-content> patients from a single centre.<\/jats:p><\/jats:sec>Methods<\/jats:title>Polymerase chain reaction and direct sequencing were used to screen DNA<\/jats:styled-content> samples for DCTN<\/jats:italic><\/jats:styled-content>4<\/jats:italic> variants.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 121 adult CF<\/jats:styled-content> patients from the C<\/jats:styled-content>ochin H<\/jats:styled-content>ospital CF<\/jats:styled-content> centre have been included, all of them carrying two CFTR<\/jats:italic><\/jats:styled-content> defects: 103 developed at least 1 pulmonary infection with Pa<\/jats:styled-content>, and 68 patients of them had CPA<\/jats:styled-content>. DCTN<\/jats:italic><\/jats:styled-content>4<\/jats:italic> variants were identified in 24% (29\/121) CF<\/jats:styled-content> patients with Pa<\/jats:styled-content> infection and in only 17% (3\/18) CF<\/jats:styled-content> patients with no P<\/jats:styled-content>a infection. Of the patients with CPA<\/jats:styled-content>, 29% (20\/68) had DCTN<\/jats:italic><\/jats:styled-content>4<\/jats:italic> missense variants vs 23% (8\/35) in patients without CPA<\/jats:styled-content>. Interestingly, p.Tyr<\/jats:styled-content>263Cys<\/jats:styled-content> tend to be more frequently observed in CF<\/jats:styled-content> patients with CPA<\/jats:styled-content> than in patients without CPA<\/jats:styled-content> (4\/68 vs 0\/35), and DCTN<\/jats:italic><\/jats:styled-content>4<\/jats:italic> missense variants tend to be more frequent in male CF<\/jats:styled-content> patients with CPA<\/jats:styled-content> bearing two class II<\/jats:styled-content> mutations than in male CF<\/jats:styled-content> patients without CPA<\/jats:styled-content> bearing two class II<\/jats:styled-content> mutations (P<\/jats:italic>\u2009=\u20090.06).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Our observations reinforce that DCTN<\/jats:italic><\/jats:styled-content>4<\/jats:italic> missense variants, especially p.Tyr<\/jats:styled-content>263Cys<\/jats:styled-content>, may be involved in the pathogenesis of CPA<\/jats:styled-content> in male CF<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/crj.12288","type":"journal-article","created":{"date-parts":[[2015,3,12]],"date-time":"2015-03-12T11:09:30Z","timestamp":1426158570000},"page":"777-783","source":"Crossref","is-referenced-by-count":11,"title":["DCTN<\/scp>4 as a modifier of chronic P<\/i><\/scp>seudomonas aeruginosa<\/i> infection in cystic fibrosis"],"prefix":"10.1111","volume":"10","author":[{"given":"Marion","family":"Viel","sequence":"first","affiliation":[{"name":"AP\u2010HP Laboratoire de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire Groupe Universitaire Paris Centre Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Hubert","sequence":"additional","affiliation":[{"name":"Service de Pneumologie GH Cochin\u2010Broca\u2010H\u00f4tel Dieu Universit\u00e9 Paris Descartes Paris 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