Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens

M. Chillon, T. Casals, B. Mercier, L. Bassas, W. Lissens, S. Silber, M. C. Romey -, J. Ruiz-Romero, C. Verlingue, M. Claustres, V. Nunes, C. Ferec, Xavier P. Estivill

Research output: Contribution to journalArticle

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Abstract

Background. Congenital bilateral absence of the vas deferens (CBAVD) is a form of male infertility in which mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been identified. The molecular basis of CBAVD is not completely understood. Although patients with cystic fibrosis have mutations in both copies of the CFTR gene, most patients with CBAVD have mutations in only one copy of the gene. Methods. To investigate CBAVD at the molecular level, we have characterized the mutations in the CFTR gene in 102 patients with this condition. None had clinical manifestations of cystic fibrosis. We also analyzed a DNA variant (the 5T allele) in a noncoding region of CFTR that causes reduced levels of the normal CFTR protein. Parents of patients with cystic fibrosis, patients with types of infertility other than CBAVD, and normal subjects were studied as controls. Results. Nineteen of the 102 patients with CBAVD had mutations in both copies of the CFTR gene, and none of them had the 5T allele. Fifty-four patients had a mutation in one copy of CFTR, and 34 of them (63 percent) had the 5T allele in the other CFTR gene. In 29 patients no CFTR mutations were found, but 7 of them (24 percent) had the 5T allele. In contrast, the frequency of this allele in the general population was about 5 percent. Conclusions. Most patients with CBAVD have mutations in the CFTR gene. The combination of the 5T allele in one copy of the CFTR gene with a cystic fibrosis mutation in the other copy is the most common cause of CBAVD. The 5T allele mutation has a wide range of clinical presentations, occurring in patients with CBAVD or moderate forms of cystic fibrosis and in fertile men.

Original languageEnglish
Pages (from-to)1475-1480
Number of pages6
JournalNew England Journal of Medicine
Volume332
Issue number22
DOIs
Publication statusPublished - 1995
Externally publishedYes

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Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis
Regulator Genes
Mutation
Genes
Alleles
Congenital bilateral aplasia of vas deferens
Male Infertility
Gene Frequency
Infertility
Parents

ASJC Scopus subject areas

  • Medicine(all)

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Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. / Chillon, M.; Casals, T.; Mercier, B.; Bassas, L.; Lissens, W.; Silber, S.; Romey -, M. C.; Ruiz-Romero, J.; Verlingue, C.; Claustres, M.; Nunes, V.; Ferec, C.; Estivill, Xavier P.

In: New England Journal of Medicine, Vol. 332, No. 22, 1995, p. 1475-1480.

Research output: Contribution to journalArticle

Chillon, M, Casals, T, Mercier, B, Bassas, L, Lissens, W, Silber, S, Romey -, MC, Ruiz-Romero, J, Verlingue, C, Claustres, M, Nunes, V, Ferec, C & Estivill, XP 1995, 'Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens', New England Journal of Medicine, vol. 332, no. 22, pp. 1475-1480. https://doi.org/10.1056/NEJM199506013322204
Chillon, M. ; Casals, T. ; Mercier, B. ; Bassas, L. ; Lissens, W. ; Silber, S. ; Romey -, M. C. ; Ruiz-Romero, J. ; Verlingue, C. ; Claustres, M. ; Nunes, V. ; Ferec, C. ; Estivill, Xavier P. / Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. In: New England Journal of Medicine. 1995 ; Vol. 332, No. 22. pp. 1475-1480.
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abstract = "Background. Congenital bilateral absence of the vas deferens (CBAVD) is a form of male infertility in which mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been identified. The molecular basis of CBAVD is not completely understood. Although patients with cystic fibrosis have mutations in both copies of the CFTR gene, most patients with CBAVD have mutations in only one copy of the gene. Methods. To investigate CBAVD at the molecular level, we have characterized the mutations in the CFTR gene in 102 patients with this condition. None had clinical manifestations of cystic fibrosis. We also analyzed a DNA variant (the 5T allele) in a noncoding region of CFTR that causes reduced levels of the normal CFTR protein. Parents of patients with cystic fibrosis, patients with types of infertility other than CBAVD, and normal subjects were studied as controls. Results. Nineteen of the 102 patients with CBAVD had mutations in both copies of the CFTR gene, and none of them had the 5T allele. Fifty-four patients had a mutation in one copy of CFTR, and 34 of them (63 percent) had the 5T allele in the other CFTR gene. In 29 patients no CFTR mutations were found, but 7 of them (24 percent) had the 5T allele. In contrast, the frequency of this allele in the general population was about 5 percent. Conclusions. Most patients with CBAVD have mutations in the CFTR gene. The combination of the 5T allele in one copy of the CFTR gene with a cystic fibrosis mutation in the other copy is the most common cause of CBAVD. The 5T allele mutation has a wide range of clinical presentations, occurring in patients with CBAVD or moderate forms of cystic fibrosis and in fertile men.",
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T1 - Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens

AU - Chillon, M.

AU - Casals, T.

AU - Mercier, B.

AU - Bassas, L.

AU - Lissens, W.

AU - Silber, S.

AU - Romey -, M. C.

AU - Ruiz-Romero, J.

AU - Verlingue, C.

AU - Claustres, M.

AU - Nunes, V.

AU - Ferec, C.

AU - Estivill, Xavier P.

PY - 1995

Y1 - 1995

N2 - Background. Congenital bilateral absence of the vas deferens (CBAVD) is a form of male infertility in which mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been identified. The molecular basis of CBAVD is not completely understood. Although patients with cystic fibrosis have mutations in both copies of the CFTR gene, most patients with CBAVD have mutations in only one copy of the gene. Methods. To investigate CBAVD at the molecular level, we have characterized the mutations in the CFTR gene in 102 patients with this condition. None had clinical manifestations of cystic fibrosis. We also analyzed a DNA variant (the 5T allele) in a noncoding region of CFTR that causes reduced levels of the normal CFTR protein. Parents of patients with cystic fibrosis, patients with types of infertility other than CBAVD, and normal subjects were studied as controls. Results. Nineteen of the 102 patients with CBAVD had mutations in both copies of the CFTR gene, and none of them had the 5T allele. Fifty-four patients had a mutation in one copy of CFTR, and 34 of them (63 percent) had the 5T allele in the other CFTR gene. In 29 patients no CFTR mutations were found, but 7 of them (24 percent) had the 5T allele. In contrast, the frequency of this allele in the general population was about 5 percent. Conclusions. Most patients with CBAVD have mutations in the CFTR gene. The combination of the 5T allele in one copy of the CFTR gene with a cystic fibrosis mutation in the other copy is the most common cause of CBAVD. The 5T allele mutation has a wide range of clinical presentations, occurring in patients with CBAVD or moderate forms of cystic fibrosis and in fertile men.

AB - Background. Congenital bilateral absence of the vas deferens (CBAVD) is a form of male infertility in which mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been identified. The molecular basis of CBAVD is not completely understood. Although patients with cystic fibrosis have mutations in both copies of the CFTR gene, most patients with CBAVD have mutations in only one copy of the gene. Methods. To investigate CBAVD at the molecular level, we have characterized the mutations in the CFTR gene in 102 patients with this condition. None had clinical manifestations of cystic fibrosis. We also analyzed a DNA variant (the 5T allele) in a noncoding region of CFTR that causes reduced levels of the normal CFTR protein. Parents of patients with cystic fibrosis, patients with types of infertility other than CBAVD, and normal subjects were studied as controls. Results. Nineteen of the 102 patients with CBAVD had mutations in both copies of the CFTR gene, and none of them had the 5T allele. Fifty-four patients had a mutation in one copy of CFTR, and 34 of them (63 percent) had the 5T allele in the other CFTR gene. In 29 patients no CFTR mutations were found, but 7 of them (24 percent) had the 5T allele. In contrast, the frequency of this allele in the general population was about 5 percent. Conclusions. Most patients with CBAVD have mutations in the CFTR gene. The combination of the 5T allele in one copy of the CFTR gene with a cystic fibrosis mutation in the other copy is the most common cause of CBAVD. The 5T allele mutation has a wide range of clinical presentations, occurring in patients with CBAVD or moderate forms of cystic fibrosis and in fertile men.

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U2 - 10.1056/NEJM199506013322204

DO - 10.1056/NEJM199506013322204

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

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