• PMID: 23378603
• Gene Name: CFTR
• Condition: CBAVD, other CFTR-related disorders
• Association: 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' genotype, a CFTR analysis should be considered in their partners in order to identify CF carrier co
• Mutation: p.Arg117His
• Population size: 179
• Population details: 179 non-newborn French individuals (83 isolated CBAVD, 67 other CFTR-related phenotypes, 44 CBAVD with pulmonary and/or pancreatic symptoms, 12 asymptomatic cases)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: CBAVD and other CFTR-related disorders

CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders

Thauvin-Robinet C, Munck A, Huet F, de Becdelièvre A, Jimenez C, Lalau G, Gautier E, Rollet J, Flori J, Nové-Josserand R, Soufir JC, Haloun A, Hubert D, Houssin E, Bellis G, Rault G, David A, Janny L, Chiron R, Rives N, Hairion D, Collignon P, Valeri A, Karsenty G, Rossi A, Audrézet MP, Férec C, Leclerc J, Georges Md, Claustres M, Bienvenu T, Gérard B, Boisseau P, Cabet-Bey F, Cheillan D, Feldmann D, Clavel C, Bieth E, Iron A, Simon-Bouy B, Izard V, Steffann J, Viville S, Costa C, Drouineaud V, Fauque P, Binquet C, Bonithon-Kopp C, Morris MA, Faivre L, Goossens M, Roussey M, Girodon E; collaborating working group on p.Arg117His.

BACKGROUND: The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) 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. METHODS: Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.Arg117His and a second CFTR mutation referred for symptoms or family history, by all French molecular genetics laboratories, referring physicians, CF care centres and infertility clinics. RESULTS: 97% of the patients had the intronic T7 normal variant in cis 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. CONCLUSIONS: 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' genotype, a CFTR analysis should be considered in their partners in order to identify CF carrier couples and offer PND or PGD. FAU - Thauvin-Robinet, Christel AU - Thauvin-Robinet C AD - Centre de Génétique, Hôpital d'Enfants, 10 Bd du Maréchal de Lattre de Tassigny, Dijon cedex 21034, France. christel.thauvin@chu-dijon.fr FAU - Munck, Anne AU - Munck A FAU - Huet, Frédéric AU - Huet F FAU - de Becdelièvre, Alix AU - de Becdelièvre A FAU - Jimenez, Clément AU - Jimenez C FAU - Lalau, Guy AU - Lalau G FAU - Gautier, Elodie AU - Gautier E FAU - Rollet, Jacques AU - Rollet J FAU - Flori, Jean AU - Flori J FAU - Nové-Josserand, Raphaëlle AU - Nové-Josserand R FAU - Soufir, Jean-Claude AU - Soufir JC FAU - Haloun, Alain AU - Haloun A FAU - Hubert, Dominique AU - Hubert D FAU - Houssin, Elise AU - Houssin E FAU - Bellis, Gil AU - Bellis G FAU - Rault, Gilles AU - Rault G FAU - David, Albert AU - David A FAU - Janny, Laurent AU - Janny L FAU - Chiron, Raphaël AU - Chiron R FAU - Rives, Nathalie AU - Rives N FAU - Hairion, Dominique AU - Hairion D FAU - Collignon, Patrick AU - Collignon P FAU - Valeri, Antoine AU - Valeri A FAU - Karsenty, Gilles AU - Karsenty G FAU - Rossi, Annick AU - Rossi A FAU - Audrézet, Marie-Pierre AU - Audrézet MP FAU - Férec, Claude AU - Férec C FAU - Leclerc, Julie AU - Leclerc J FAU - Georges, Marie des AU - Georges Md FAU - Claustres, Mireille AU - Claustres M FAU - Bienvenu, Thierry AU - Bienvenu T FAU - Gérard, Bénédicte AU - Gérard B FAU - Boisseau, Pierre AU - Boisseau P FAU - Cabet-Bey, Faïza AU - Cabet-Bey F FAU - Cheillan, David AU - Cheillan D FAU - Feldmann, Delphine AU - Feldmann D FAU - Clavel, Christine AU - Clavel C FAU - Bieth, Eric AU - Bieth E FAU - Iron, Albert AU - Iron A FAU - Simon-Bouy, Brigitte AU - Simon-Bouy B FAU - Izard, Vincent AU - Izard V FAU - Steffann, Julie AU - Steffann J FAU - Viville, Stéphane AU - Viville S FAU - Costa, Catherine AU - Costa C FAU - Drouineaud, Véronique AU - Drouineaud V FAU - Fauque, Patricia AU - Fauque P FAU - Binquet, Christine AU - Binquet C FAU - Bonithon-Kopp, Claire AU - Bonithon-Kopp C FAU - Morris, Mike A AU - Morris MA FAU - Faivre, Laurence AU - Faivre L FAU - Goossens, Michel AU - Goossens M FAU - Roussey, Michel AU - Roussey M