{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:16:14Z","timestamp":1791288974616,"version":"4.3.0"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,2,27]]},"abstract":"<jats:p>\n                    Thioredoxins belong to a large family of enzymatic proteins that function as general protein disulfide reductases, therefore participating in several cellular processes via redox-mediated reactions. So far, none of the 18 members of this family has been involved in human pathology. Here we identified\n                    <jats:italic>TXNDC3<\/jats:italic>\n                    , which encodes a thioredoxin\u2013nucleoside diphosphate kinase, as a gene implicated in primary ciliary dyskinesia (PCD), a genetic condition characterized by chronic respiratory tract infections, left\u2013right asymmetry randomization, and male infertility. We show that the disease, which segregates as a recessive trait, results from the unusual combination of the following two transallelic defects: a nonsense mutation and a common intronic variant found in 1% of control chromosomes. This variant affects the ratio of two physiological\n                    <jats:italic>TXNDC3<\/jats:italic>\n                    transcripts: the full-length isoform and a novel isoform,\n                    <jats:italic>TXNDC3d7<\/jats:italic>\n                    , carrying an in-frame deletion of exon 7.\n                    <jats:italic>In vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    expression data unveiled the physiological importance of\n                    <jats:italic>TXNDC3d7<\/jats:italic>\n                    (whose expression was reduced in the patient) and the corresponding protein that was shown to bind microtubules. PCD is known to result from defects of the axoneme, an organelle common to respiratory cilia, embryonic nodal cilia, and sperm flagella, containing dynein arms, with, to date, the implication of genes encoding dynein proteins. Our findings, which identify a another class of molecules involved in PCD, disclose the key role of TXNDC3 in ciliary function; they also point to an unusual mechanism underlying a Mendelian disorder, which is an SNP-induced modification of the ratio of two physiological isoforms generated by alternative splicing.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0611405104","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T00:04:11Z","timestamp":1172016251000},"page":"3336-3341","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":174,"title":["A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia"],"prefix":"10.1073","volume":"104","author":[{"given":"B\u00e9n\u00e9dicte","family":"Duriez","sequence":"first","affiliation":[{"name":"*Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 654, F-94000 Cr\u00e9teil, France;"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris 12, IFR10, F-94000 Cr\u00e9teil, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Duquesnoy","sequence":"additional","affiliation":[{"name":"*Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 654, F-94000 Cr\u00e9teil, France;"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris 12, IFR10, F-94000 Cr\u00e9teil, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Escudier","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 651, F-94000 Cr\u00e9teil, France;"},{"name":"Universit\u00e9 Pierre et Marie Curie, Paris 75005, France;"},{"name":"Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re, D\u00e9partement de G\u00e9n\u00e9tique-Cytog\u00e9n\u00e9tique-Embryologie, Assistance 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France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Marcos","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris 12, IFR10, F-94000 Cr\u00e9teil, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Vojtek","sequence":"additional","affiliation":[{"name":"Laboratoire de Microscopie \u00e9lectronique, Service d'Anatomie Pathologique, Centre Hospitalier Intercommunal de Cr\u00e9teil, F-94000 Cr\u00e9teil, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Bercher","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Math\u00e9matiques, Ecole Sup\u00e9rieure d'Ing\u00e9nieurs en Electronique et Electrotechnique, Cit\u00e9 Descartes, F-93162 Noisy-Le-Grand, 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