Une forme de cryptorchidie d’origine génétique: le syndrome de persistance des canaux de Müller

Persistent Müllerian duct syndrome (PMDS), a rare form of male peudohermaphrodism, is characterized by lack of regression of Müllerian derivatives. These patients are externally phenotypic males in whom the presence of a uterus and Fallopian tubes is discovered during surgical correction of cryptorchidism and/or inguinal hernia. Molecular studies, in a total of 76 PMDS families, were performed by automatic sequencing after amplification by polymerase chain reaction (PCR) of different parts of the gene. AMH, synthesized by Sertoli cells, is a member of the Transforming Growth Factor-β superfamily. The 560 amino-acid glycoprotein is formed by two 70 kDa monomers linked by disulfide bonds. This hormone is cleaved at a proteolytic site 109 amino acids upstream of the C-terminus, yielding the bioactive C-terminal domain and a N-terminus which is not itself bioactive, but which enhances the bioactivity of the C-terminus. The gene, composed of five exons, is located on chromosome 19 (band p13.3). AMH gene mutations are present on the whole length of the gene in 47% of PMDS families. Sixty-one per cent were homozygous due to a high proportion of patients from Arabic or Mediterranean countries, characterized by a high rate of consanguinity. The serum AMH level, assessed by a commercially available enzyme immunoassay technique (ELISA), is extremely low in the great majority of patients, even before puberty when AMH levels are normally high. AMH binds to two distinct membrane-bound receptors, both serine/threonine kinases. The type II AMH receptor (AMHR-II) binds to the ligand, and this complex recruits receptor type I, which acts as a signal transducer by activating specific cytoplasmic substrates, the Smad molecules. AMHR-II, coded by a 8 kbp gene on chromosome 12 (band q13), contains 11 exons. Exons 1–3 encode the extracellular domain, exon 4 encodes the transmembrane part and exons 5–11 encode the intracellular serine/threonine kinase domain. An AMHR-II mutation was detected in 38% of PMDS families, characterized by a normal AMH level for the patient’s age. A particular mutation, a deletion of 27 bp in exon 10, was present in 45% of families of this group. No mutation of either AMH or the AMHR-II gene could be detected in 11 PMDS families.