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). DESIGN: Descriptive, controlled study. SETTING: Tertiary academic hospital genetics laboratory and private in vitro fertilization (IVF) clinic. PATIENT(S): 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. INTERVENTION(S): Clinical evaluation and treatment, genetical screenings. MAIN OUTCOME MEASURE(S): Clinical data, biochemical assays, spermiogram analysis, testicle biopsy, intracytoplasmic sperm injection (ICSI) outcome, and CFTR whole gene mutation screening and IVS8T polymorphism. RESULT(S): 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. CONCLUSION(S): 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.
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). DESIGN: Descriptive, controlled study. SETTING: Tertiary academic hospital genetics laboratory and private in vitro fertilization (IVF) clinic. PATIENT(S): 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. INTERVENTION(S): Clinical evaluation and treatment, genetical screenings. MAIN OUTCOME MEASURE(S): Clinical data, biochemical assays, spermiogram analysis, testicle biopsy, intracytoplasmic sperm injection (ICSI) outcome, and CFTR whole gene mutation screening and IVS8T polymorphism. RESULT(S): 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. CONCLUSION(S): 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.