Correspondence
High Frequency of the R117H Cystic Fibrosis Mutation in Patients with Congenital Absence of the Vas Deferens
N Engl J Med 1993; 328:446-447February 11, 1993
- Article
To the Editor:
We have previously described an increased frequency of the δF508 mutation of the cystic fibrosis gene in a group of patients with congenital absence of the vas deferens1. This suggested that patients heterozygous for the δF508 mutation may have a mutation on another allele. We have looked for other mutations of the cystic fibrosis gene in a group of 23 patients with congenital absence of the vas deferens, 11 of whom were heterozygous for the δF508 mutation. We found that four patients were compound heterozygotes, all having an R117H mutation in exon 4 of the cystic fibrosis gene: three patients had a δF508/R117H cystic fibrosis genotype, and the fourth had an R117H/2322delG genotype.
All the patients were seen because of sterility, and all had undergone scrotal exploration, which had shown bilateral absence of the vas deferens. They had no pulmonary evidence of cystic fibrosis. Five patients without the δF508 mutation had unilateral renal agenesis in addition to absence of the vas deferens.
The 27 exons of the cystic fibrosis gene were analyzed in each of the 23 patients by examination of single-strand conformation polymorphisms of DNA after amplification with the polymerase chain reaction2. The amplified single-stranded DNAs corresponding to the different exons were analyzed by gel electrophoresis; they were sequenced if their mobility was shifted from the normal position.
Three patients had the R117H mutation of exon 4 described by Dean et al.3 in addition to the δF508 mutation (exon 10). A fourth patient had an R117H mutation in addition to a novel mutation in exon 13 (2322delG). These four unrelated patients (35, 32, 32, and 39 years old) had normal chest films. Their values for forced expiratory volume in one second were 96, 112, 101, and 87 percent, respectively. Their sweat chloride values were 90, 78, 70, and 62 mmol per liter, respectively (normal, ≤ 60). None of them had unilateral renal agenesis. In one patient, we verified that the allele with the δF508 mutation was transmitted by one parent and that the allele with the R117H mutation was transmitted by the other parent.
The frequency of cystic fibrosis genotypes with an R117H mutation appears to be high (4 of 18) among patients with congenital absence of the vas deferens without unilateral renal agenesis. Using a similar technique, Anguiano and colleagues found a mobility shift of exon 4 in patients with congenital bilateral absence of the vas deferens,4 and Kristidis and colleagues have already suggested that the R117H mutation might correspond to mild forms of cystic fibrosis5.
5 ReferencesRadj Gervais, M.D.
Viviane Dumur, Ph.D.
Jean-Marc Rigot, M.D.
Jean-Jacques Lafitte, M.D.
Philippe Roussel, M.D.
Centre Hospitalier Regional, 59045 Lille, FranceMireille Claustres, M.D.
Jacques Demaille, M.D.
Centre Hospitalier Regional, 34033 Montpellier, France1
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- Citing Articles (22)
Citing Articles
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Peter D. FIELD, Nicole J. MARTIN. (2011) CFTR mutation screening in an assisted reproductive clinic. Australian and New Zealand Journal of Obstetrics and Gynaecologyno-no
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Katherine D. Schoyer, Fred Gilbert, Zev Rosenwaks. (2008) Infertility and abnormal cervical mucus in two sisters who are compound heterozygotes for the cystic fibrosis (CF) ΔF508 and R117H/7T mutations. Fertility and Sterility 90:4, 1201.e19-1201.e22
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Mireille Claustres. (2005) Molecular pathology of the CFTR locus in male infertility. Reproductive BioMedicine Online 10:1, 14-41
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Andres Estrada, Juan C. Samper, James D. Lillich, Rahul R. Rathi, Leah S. Brault, Beth B. Albrecht, Matt M. Imel, Erin M. Senne. (2003) Azoospermia associated with bilateral segmental aplasia of the ductus deferens in a stallion. Journal of the American Veterinary Medical Association 222:12, 1740-1743
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Full Text21
ISABELLE DURIEU, FALIZA BEY-OMAR, JACQUES ROLLET, LAURENCE CALEMARD, DOMINIQUE BOGGIO, HERVE LEJEUNE, ROBERT GILLY, YVES MOREL, DENIS VITAL DURAND. (1995) Diagnostic Criteria for Cystic Fibrosis in Men with Congenital Absence of the Vas Deferens. Medicine 74:1, 42-47
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