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Absence de corrélation génotype-phénotype dans les absences de canaux déférents

Lack of correlation between reproductive tract abnormalities and CFTR gene mutations in men with absence of the vas deferens

Andrologie volume 11, pages 21–32 (2001)Cite this article

Résumé

L’absence des canaux déférents est une cause rare d’infertilité masculine associée dans 80% des cas à des mutations sur le géne de la mucoviscidose. Cependant, les corrélations entre le génotype et le phénotype anatomique des voies excrétrices du sperme ont été peu étudiées.

À partir d’une série de 47 patients porteurs d’une absence des canaux déférents, nous avons recherché les 13 mutations les plus fréquentes de la mucoviscidose, l’allèle 5T de l’intron 8 et exploré le tractus uro-génital par échographie rénale, scrotale et endorectale.

Quarante patients avaient une absence bilatérale des canaux déférents (ABCD) et 7 patients présentaient une absence unilatérale d’un canal déférent.

Trente patients (64%) étaient porteur dune anomalie d’une anomalie du gène CFTR parmi eux, 47% avaient une mutation ΔF 508 et 63% étaient porteurs de l’allèle 5T. Dixsept patients n’avaient aucune des mutations recherchées, dont 3 patients porteurs d’une agénésie rénale unilatérale et 3 patients porteurs d’une absence unilatérale d’un canal déférent.

La comparaison des phénotypes entre les différents groupes ne fait ressortir aucune différence concernant l’état des vésicules séminales, la symétrie des anomalies vésiculaires et épididymaires. On constate une différence significative des anomalies épididymaires qui sont plus fréquentes dans le groupe sans mutation que dans le groupe avec des mutations (test de chi2, p=0,01).

Les moyennes des volumes testiculaires sont significativement plus faibles entre les patients avec au moins une mutation CFTR et les patients sans mutation ou seulement avec l’allèle 5T: 15,1±4,5 ml versus 10,7±4,1 ml respectivement (p<0,001, test de Student).

En conclusion, dans les absences isolées des canaux déférents, le phénotype anatomique des voies excrétrices du sperme n’est pas corrélé au génotype de la mucoviscidose. Ces résultats suggèrent que d’autres déterminants génétiques et/ou environnementaux sont nécessaires pour rendre compte d’un mécanisme pathogénique commun à ces anomalies. Le volume testiculaire abaissé chez les patients sans mutation ou porteurs de l’allèle 5T seul suppose l’existence d’un facteur sécrétoire ou mixte (obstructif et sécrétoire) non identifié.

Abstract

Absence of the vas deferens is a rare cause of male infertility, associated with mutations in the cystic fibrosis transmembrane regulator (CFTR) gene in about 80% of cases.

Only limited published data are available concerning the correlation between genotype and reproductive tract abnormalities observed in this disease: presence or absence of seminal vesicles and parts of the epididymis, symmetrical or asymmetrical lesions, testicular volumes.

We screened 47 patients for the 13 most common CFTR mutations on the cystic fibrosis gene and for the 5-thymidine variant of the polythymidine tract of intron 8. Renal, scrotal and transrectal ultrasonography was performed in each patient to explore the testes and reproductive tract. All patients presented absence of the ampullae of the vas deferens.

Forty patients presented bilateral absence of the vas deferens and 7 presented unilateral absence of the vas deferens.

At least one mutation of the cystic fibrosis gene was present in 64% of cases: 47% had the ΔF 508 mutation and 63% had the 5T allele. No mutation was detected in seventeen patients, including 3 patients with unilateral renal agenesis and 3 patients with unilateral absence of the vas deferens.

No differences were observed for seminal vesicles and symmetry of vesicular and epididymal abnormalities between patients with or without CFTR gene mutations, but epididymal abnormalities were significantly more frequent in the group without mutation (p=0.01).

Testicular volumes were significantly lower in the patients without mutation or with the 5T allele only, than in the patients with at least one CFTR gene mutation: 10.7±4.1 ml versus 15.1±4.5 ml, respectively (p<0.001).

In conclusion, in cases of isolated absence of the vas deferens, there is no difference in sperm duct abnormalities between patients with or without CFTR gene mutation. These results suggest that other genetic or environmental determinants are required to explain a common pathogenesis for these malformations. The decreased testicular volume of patients without CFTR gene mutation or with the 5T allele only suggests the existence of an unidentified secretory or mixed factor involved in these forms of absence of the vas deferens.

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Authors and Affiliations

  1. Institut Rhônalpin, 1, rue laborde, 69500, BRON

    F. Robert & J. Rollet

  2. Hôpital Debrousse, 29, rue Soeur Bouvier, 69322, Lyon Cedex 05

    F. Bey-Omar & Y. Morel

  3. 151, avenue de Saxe, 69003, Lyon

    J. F. Lapray

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Robert, F., Bey-Omar, F., Rollet, J. et al. Absence de corrélation génotype-phénotype dans les absences de canaux déférents. Androl. 11, 21–32 (2001). https://doi.org/10.1007/BF03034392

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Basic and Clinical Andrology

ISSN: 2051-4190