title: CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders.
abstract: 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.
authors: Centre de Génétique, Hôpital d'Enfants, 10 Bd du Maréchal de Lattre de Tassigny, Dijon cedex 21034, France. christel.thauvin@chu-dijon.fr
authors: Christel
authors: C
authors: Thauvin-Robinet
authors: Anne
authors: A
authors: Munck
authors: Frédéric
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authors: Huet
authors: Alix
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authors: de Becdelièvre
authors: Clément
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authors: Jimenez
authors: Guy
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authors: Lalau
authors: Elodie
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authors: Gautier
authors: Jacques
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authors: Rollet
authors: Jean
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authors: Flori
authors: Raphaëlle
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authors: Nové-Josserand
authors: Jean-Claude
authors: JC
authors: Soufir
authors: Alain
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authors: Haloun
authors: Dominique
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authors: Hubert
authors: Elise
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authors: Houssin
authors: Gil
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authors: Bellis
authors: Gilles
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authors: Rault
authors: Albert
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authors: David
authors: Laurent
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authors: Janny
authors: Raphaël
authors: R
authors: Chiron
authors: Nathalie
authors: N
authors: Rives
authors: Dominique
authors: D
authors: Hairion
authors: Patrick
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authors: Collignon
authors: Antoine
authors: A
authors: Valeri
authors: Gilles
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authors: Karsenty
authors: Annick
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authors: Rossi
authors: Marie-Pierre
authors: MP
authors: Audrézet
authors: Claude
authors: C
authors: Férec
authors: Julie
authors: J
authors: Leclerc
authors: Marie des
authors: Md
authors: Georges
authors: Mireille
authors: M
authors: Claustres
authors: Thierry
authors: T
authors: Bienvenu
authors: Bénédicte
authors: B
authors: Gérard
authors: Pierre
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authors: Boisseau
authors: Faïza
authors: F
authors: Cabet-Bey
authors: David
authors: D
authors: Cheillan
authors: Delphine
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authors: Feldmann
authors: Christine
authors: C
authors: Clavel
authors: Eric
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authors: Bieth
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authors: Iron
authors: Brigitte
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authors: Simon-Bouy
authors: Vincent
authors: V
authors: Izard
authors: Julie
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authors: Steffann
authors: Stéphane
authors: S
authors: Viville
authors: Catherine
authors: C
authors: Costa
authors: Véronique
authors: V
authors: Drouineaud
authors: Patricia
authors: P
authors: Fauque
authors: Christine
authors: C
authors: Binquet
authors: Claire
authors: C
authors: Bonithon-Kopp
authors: Mike A
authors: MA
authors: Morris
authors: Laurence
authors: L
authors: Faivre
authors: Michel
authors: M
authors: Goossens
authors: Michel
authors: M
authors: Roussey
authors: Emmanuelle
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authors: Girodon
mesh_terms: D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007248:Infertility, Male / Q000150:complications / Q000235:genetics; D008297:Male; D052801:Male Urogenital Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D059645:Mutation Rate; D010641:Phenotype; D011296:Prenatal Diagnosis; D013542:Sweat / Q000737:chemistry; D014649:Vas Deferens / Q000002:abnormalities / Q000473:pathology
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator