title: Analysis of cystic fibrosis transmembrane conductance regulator gene mutations in patients with congenital absence of the uterus and vagina.
abstract: The relationship between cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations and congenital absence of the uterus and vagina (CAUV) was examined. CFTR mutations have previously been associated with congenital bilateral absence of the vas deferens (CBAVD). CBAVD is caused by a disruption in the vas deferens, a Wolffian duct derivative. Because the embryologic development of the Müllerian ducts directly depends on the prior normal development of the Wolffian ducts, the same gene products may be necessary for normal embryologic development of both ductal systems. This study evaluated the role of CFTR mutations in the development of CAUV. DNA samples from 25 patients with CAUV were tested for the presence of 33 of the most common CFTR mutations. Protein-coding DNA fragments from the CFTR gene were amplified in vitro by the polymerase chain reaction (PCR) and analyzed for mutations using allele-specific oligonucleotide (ASO) probes. Two patients were heterozygous for CFTR mutations. One was heterozygous for the W1282X mutation and the other was heterozygous for the DeltaF508 mutation. The incidence of the 33 CFTR mutations found in the patients with CAUV (8%) was twice that found in the general population (4%), but much less than the incidence of CFTR mutations in men with CBAVD (80%). This data suggests that it is unlikely for CFTR mutations to cause CAUV in females as they cause CBAVD in some males. Furthermore, the data suggest that CAUV in females may be the same disorder as CBAVD in males who do not have CFTR mutations.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Lorna S
authors.initials: LS
authors.lastname: Timmreck
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gray
authors.forename: Barbara
authors.initials: B
authors.lastname: Handelin
authors.forename: Bernice
authors.initials: B
authors.lastname: Allito
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rohlfs
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Davis
authors.forename: Gita
authors.initials: G
authors.lastname: Gidwani
authors.forename: Richard H
authors.initials: RH
authors.lastname: Reindollar
mesh_terms: D000483:Alleles; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D007621:Karyotyping; D008297:Male; D009154:Mutation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000235:genetics; D014591:Uterine Diseases / Q000235:genetics; D014599:Uterus / Q000002:abnormalities*; D014621:Vagina / Q000002:abnormalities*; D014649:Vas Deferens / Q000002:abnormalities
chemical_list: C505032:CFTR protein, human; D009841:Oligonucleotides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA