Azoospermie et connexines GJB2 et GJB6 : étude clinique, histologique et génétique

Introduction
The connexins GJB2 and GJB6, transmembrane proteins, play a key role in intercellular communication. Mutations in their genes are well known in non-syndromic congenital deafness. Although their involvement in ovarian function has been described, their role at the testicular level is less well established. We describe a patient with a rare association between congenital hearing loss linked to a compound mutation of the connexins (GJB2 and GJB6) and non-obstructive azoospermia, suggesting a possible common genetic link.
Case Report
A 27-year-old man, with bilateral sensorineural hearing loss since childhood, was referred for primary infertility. The andrological workup revealed: LH: 3.6 IU/L, FSH: 12.4 IU/L (< 12), Testosterone: 15 mmol/L (8-30), inhibin B: 98 g/L (105-439), and azoospermia. Scrotal ultrasound showed a moderate bilateral hydrocele and testes measuring 12 and 7 ml. A testicular biopsy revealed Sertoli cell-only syndrome (SCOS) on the left and hypospermia on the right. The karyotype was XY, with no Y microdeletion or cystic fibrosis mutation. A heterozygous Δ(GJB6-D13S1830) deletion of the GJB6 gene and an associated GJB2 mutation (c.35 del G variant) were identified.
Discussion: The link between connexins 37 and 43 in hearing and ovarian function is well documented. This rare observation raises the possibility of a connexin-mediated pathophysiological mechanism affecting both hearing and spermatogenesis. Further studies are needed to determine whether this is a coincidence or a new syndromic entity.