title: Novel cause of hereditary obstructive azoospermia: a T2 allele in the CFTR gene.
abstract: Congenital bilateral absence of the vas deferens (CBAVD) is a frequent cause of obstructive azoospermia, and caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A novel TG(13)T(2) allele was identified in a CBAVD patient with no clinical cystic fibrosis phenotype, normal pancreatic function, normal sweat chloride concentrations and no Y chromosome microdeletions. This case was studied for CFTR mutations, IVS8-poly(T), and M470V exon 10 missense polymorphism. One novel allele was detected in the (TG)(m)(T)(n) loci that had not been reported previously. This patient carried a [TG(11)T(9); R117H; p.Met470Val] haplotype on the other chromosome. Since the TG(13)T(2) allele was a compound heterozygote with R117H mutation, it was difficult to judge the severity of this allele. To better understand the complex regulation of exon 9 splicing, the levels of correctly spliced CFTR transcripts in CFTR-expressing epithelial cells derived from vas deferens and epididymis were analysed. These data emphasize the role of the T2 allele in CBAVD, and identify the T2 allele as a severe CBAVD disease-causing mutation. According to the data, the longer (TG)(m) polymorphic tract increases the proportion of transcripts with exon 9 deletion (9-), but only when activated by the short T allele.
authors.affiliation: Laboratory for Prenatal Medicine and Gynecologic Oncology, Department of Medicine, University of Basel, Switzerland. radpourr@uhbs.ch
authors.forename: Ramin
authors.initials: R
authors.lastname: Radpour
authors.forename: Elahe
authors.initials: E
authors.lastname: Taherzadeh-Fard
authors.forename: Hamid
authors.initials: H
authors.lastname: Gourabi
authors.forename: Sahar
authors.initials: S
authors.lastname: Aslani
authors.forename: Ahmad
authors.initials: A
authors.lastname: Vosough Dizaj
authors.forename: Ali
authors.initials: A
authors.lastname: Aslani
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D053713:Azoospermia / Q000235:genetics*; D001483:Base Sequence; D019295:Computational Biology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005091:Exons; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012326:RNA Splicing
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA