title: Outcome of intracytoplasmic sperm injection for a couple in which the man is carrier of CFTR p.[R74W;V201M;D1270N] and p.P841R mutations and his spouse a heterozygous carrier of p.F508del mutation of the cystic fibrosis transmembrane conductance regulator gene.
abstract: OBJECTIVE
  To document the phenotype associated with the p.[R74W;V201M;D1270N] and p.P841R mutations of cystic fibrosis transmembrane conductance regulator (CFTR) gene.
  
  
  METHODS
  Case report.
  
  
  METHODS
  Biology and medicine of reproduction in a university hospital.
  
  
  METHODS
  A couple in which the man is carrier of the triple mutant p.[R74W;V201M;D1270N] allele in trans to p.P841R mutation and his spouse a heterozygous carrier for the severe p.F508del mutation of the CFTR gene, who became pregnant after intracytoplasmic sperm injection (ICSI) with twins.
  
  
  METHODS
  Genetic counseling; CFTR gene sequencing; ICSI; children's follow-up.
  
  
  METHODS
  First report of a male phenotype associated with the p.P841R mutation.
  
  
  RESULTS
  The triple mutant p.[R74W;V201M;D1270N] allele associated with the unknown p.P841R mutations were detected in this man with congenital bilateral absence of the vas deferens, which may presume p.P841R as a severe mutation. After genetic counseling, the couple preferred prenatal diagnosis after ICSI than preimplantation genetic diagnosis, which revealed that the boys were both carriers of p.[R74W;V201M;D1270N] and p.F508del mutations. They are now 4 years old and show normal growth without nutritional deficiency.
  
  
  CONCLUSIONS
  This case report documents for the first time a male phenotype associated with the p.P841R mutation and underlines the difficulties in counseling a man with congenital bilateral absence of the vas deferens carrying uncommon mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene before ICSI.
authors.affiliation: CHU Clermont-Ferrand, Biologie du Développement et de la Reproduction, CECOS, Hôtel Dieu, Clermont Ferrand, France. fbrugnon@chu-clermontferrand.fr
authors.forename: Florence
authors.initials: F
authors.lastname: Brugnon
authors.forename: Frederic
authors.initials: F
authors.lastname: Bilan
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Heraud
authors.forename: Genevieve
authors.initials: G
authors.lastname: Grizard
authors.forename: Laurent
authors.initials: L
authors.lastname: Janny
authors.forename: Isabelle
authors.initials: I
authors.lastname: Creveaux
mesh_terms: D000328:Adult; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D050498:Live Birth; D008297:Male; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011272:Pregnancy, Multiple; D011296:Prenatal Diagnosis; D020554:Sperm Injections, Intracytoplasmic; D014427:Twins; D014564:Urogenital Abnormalities / Q000175:diagnosis / Q000235:genetics*; D014649:Vas Deferens / Q000002:abnormalities*
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator