title: A novel missense mutation P1290S at exon-20 of the CFTR gene in a Portuguese patient with congenital bilateral absence of the vas deferens.
abstract: OBJECTIVE
  To report a novel cystic fibrosis transmembrane conductance regulator (CFTR) gene missense mutation in a compound heterozygote with congenital bilateral absence of the vas deferens (CBAVD).
  
  
  METHODS
  Descriptive, controlled study.
  
  
  METHODS
  Tertiary academic hospital genetics laboratory and private in vitro fertilization (IVF) clinic.
  
  
  METHODS
  One 46-year-old man with CBAVD and no clinical cystic fibrosis (CF) phenotype as indicated by the advanced age at diagnosis, absence of chronic airways and gastrointestinal disease, and normal pancreatic function and sweat chloride concentration. Genomic blood DNA from the patient's parents was analyzed to perform family studies, and 109 fertile men, 32 patients with CBAVD, 15 children carriers of one CFTR mutation, and 5 patients with CF were used to rule out polymorphism.
  
  
  METHODS
  Clinical evaluation and treatment, genetical screenings.
  
  
  METHODS
  Clinical data, biochemical assays, spermiogram analysis, testicle biopsy, intracytoplasmic sperm injection (ICSI) outcome, and CFTR whole gene mutation screening and IVS8T polymorphism.
  
  
  RESULTS
  The DNA analysis revealed a 7T/7T homozygote at IVS8-T, with a 4000C-->T change (P1290S) in exon 20 of the CFTR gene, which was inherited from the patient's father. It was associated with a 3272-26A-->G mutation in the other allele that was inherited from his mother.
  
  
  CONCLUSIONS
  The novel P1290S missense CFTR mutation causes an amino acid change in a highly conserved region of the CFTR protein that controls channel opening. Pathogenicity is suggested by development of CBAVD in association with a mild CFTR mutation.
authors.affiliation: Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Grangeia
authors.forename: Filipa
authors.initials: F
authors.lastname: Carvalho
authors.forename: Susana
authors.initials: S
authors.lastname: Fernandes
authors.forename: Joaquina
authors.initials: J
authors.lastname: Silva
authors.forename: Mário
authors.initials: M
authors.lastname: Sousa
authors.forename: Alberto
authors.initials: A
authors.lastname: Barros
mesh_terms: D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005192:Family Health; D005820:Genetic Testing; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D011174:Portugal; D014649:Vas Deferens / Q000002:abnormalities*
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator