{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T13:35:41Z","timestamp":1770903341456,"version":"3.50.1"},"reference-count":20,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2013,1,2]]},"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (<jats:italic>CFTR<\/jats:italic>) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in newborns screened for CF has created a dilemma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.Arg117His and a second <jats:italic>CFTR<\/jats:italic> mutation referred for symptoms or family history, by all French molecular genetics laboratories, referring physicians, CF care centres and infertility clinics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>97% of the patients had the intronic T7 normal variant in <jats:italic>cis<\/jats:italic> with p.Arg117His. 89% patients were male, with CBAVD being the reason for referral in 76%. In 166\/179 patients with available detailed clinical features, final diagnoses were: four late-onset marked pulmonary disease, 83 isolated CBAVD, 67 other CFTR-related phenotypes, including 44 CBAVD with pulmonary and\/or pancreatic symptoms and 12 asymptomatic cases. Respiratory symptoms were observed in 30% of the patients, but the overall phenotype was mild. No correlation was observed between sweat chloride concentrations and disease severity. Five couples at risk of CF offspring were identified and four benefited from prenatal or preimplantation genetic diagnoses (PND or PGD). Eight children were born, including four who were compound heterozygous for p.Arg117His and one with a severe CF mutation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Patients with CBAVD carrying p.Arg117His and a severe CF mutation should benefit from a clinical evaluation and follow-up. Depending on the CBAVD patients\u2019 genotype, a <jats:italic>CFTR<\/jats:italic> analysis should be considered in their partners in order to identify CF carrier couples and offer PND or PGD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2012-101427","type":"journal-article","created":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T21:40:44Z","timestamp":1359754844000},"page":"220-227","source":"Crossref","is-referenced-by-count":28,"title":["CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders"],"prefix":"10.1136","volume":"50","author":[{"given":"Christel","family":"Thauvin-Robinet","sequence":"first","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares des \u00ab Anomalies du D\u00e9veloppement et des syndromes malformatifs \u00bb de la r\u00e9gion Est, H\u00f4pital d'Enfants, CHU Dijon, Dijon, France"},{"name":"EA 4271 GAD, IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Munck","sequence":"additional","affiliation":[{"name":"AFDPHE, Paris, France"},{"name":"CRCM P\u00e9diatrique, Assistance Publique-H\u00f4pitaux de Paris\u2014Universit\u00e9 Paris 7, H\u00f4pital Robert Debr\u00e9, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Huet","sequence":"additional","affiliation":[{"name":"EA 4271 GAD, IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"},{"name":"AFDPHE, Paris, France"},{"name":"CRCM\u2014Service de P\u00e9diatrie 1, H\u00f4pital d'Enfants, CHU Dijon, Dijon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alix","family":"de Becdeli\u00e8vre","sequence":"additional","affiliation":[{"name":"Service de Biochimie-G\u00e9n\u00e9tique et Inserm U955 \u00e9quipe 11, Groupe hospitalier Henri Mondor, APHP, Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e9ment","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Service de Biologie de la reproduction, Maternit\u00e9 du Bocage, CHU Dijon, Dijon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Lalau","sequence":"additional","affiliation":[{"name":"P\u00f4le de Biochimie et Biologie Mol\u00e9culaire, Centre de Biologie Pathologie, CHU de Lille, Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elodie","family":"Gautier","sequence":"additional","affiliation":[{"name":"Inserm, CIE1, Dijon, France"},{"name":"CHRU Dijon, Centre d'Investigation Clinique\u2014Epid\u00e9miologique\/Essais cliniques, Dijon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Rollet","sequence":"additional","affiliation":[{"name":"Service d'Assistance M\u00e9dicale \u00e0 la Procr\u00e9ation, Clinique du Val d'Ouest, 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A","family":"Morris","sequence":"additional","affiliation":[{"name":"Laboratoire de Diagnostic mol\u00e9culaire, Service de M\u00e9decine G\u00e9n\u00e9tique, H\u00f4pitaux Universitaires de Gen\u00e8ve, Gen\u00e8ve, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Faivre","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares des \u00ab Anomalies du D\u00e9veloppement et des syndromes malformatifs \u00bb de la r\u00e9gion Est, H\u00f4pital d'Enfants, CHU Dijon, Dijon, France"},{"name":"EA 4271 GAD, IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Goossens","sequence":"additional","affiliation":[{"name":"Service de Biochimie-G\u00e9n\u00e9tique et Inserm U955 \u00e9quipe 11, Groupe hospitalier Henri Mondor, APHP, Cr\u00e9teil, 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Cystic fibrosis. In: Scriver CR Beaudet AL Sly WS Valle D .eds. Metabolic and molecular bases of inherited disease. 8th edn. New York: McGraw-Hill, 2001: 5121\u201388."},{"key":"2025100521305450000_50.4.220.2","doi-asserted-by":"crossref","first-page":"S86","DOI":"10.1016\/S1569-1993(11)60014-3","article-title":"Recommendations for the classification of diseases as CFTR-related disorders","volume":"10","author":"Bombieri","year":"2011","journal-title":"J Cyst Fibros"},{"key":"2025100521305450000_50.4.220.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.05.005"},{"key":"2025100521305450000_50.4.220.4","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.136"},{"key":"2025100521305450000_50.4.220.5","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90196-L"},{"key":"2025100521305450000_50.4.220.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199302113280620"},{"key":"2025100521305450000_50.4.220.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506013322204"},{"key":"2025100521305450000_50.4.220.8","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200008)16:2<143::AID-HUMU7>3.0.CO;2-J"},{"key":"2025100521305450000_50.4.220.9","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dem024"},{"key":"2025100521305450000_50.4.220.10","doi-asserted-by":"publisher","DOI":"10.1038\/ng1193-274"},{"key":"2025100521305450000_50.4.220.11","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.01.00057001"},{"key":"2025100521305450000_50.4.220.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.02.028"},{"key":"2025100521305450000_50.4.220.13","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.067215"},{"key":"2025100521305450000_50.4.220.14","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1542\/peds.23.3.545","article-title":"A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis","volume":"23","author":"Gibson","year":"1959","journal-title":"Pediatrics"},{"key":"2025100521305450000_50.4.220.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(94)70314-0"},{"key":"2025100521305450000_50.4.220.16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jcf.2005.09.009","article-title":"Delayed diagnosis of cystic fibrosis associated with p.Arg117His on a background of 7T polythymidine tract at intron 8","volume":"5","author":"Peckham","year":"2006","journal-title":"J Cyst Fibros"},{"key":"2025100521305450000_50.4.220.17","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-0496(199605)21:5<267::AID-PPUL1>3.0.CO;2-K"},{"key":"2025100521305450000_50.4.220.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2005.11.005"},{"key":"2025100521305450000_50.4.220.19","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh083"},{"key":"2025100521305450000_50.4.220.20","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20054"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmedgenet-2012-101427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T04:31:04Z","timestamp":1759725064000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmedgenet-2012-101427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,1]]},"references-count":20,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2013,3,13]]},"published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1136\/jmedgenet-2012-101427"],"URL":"https:\/\/doi.org\/10.1136\/jmedgenet-2012-101427","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,1]]}}}