OR12-3 PHENOTYPE GENOTYPE CORRELATIONS IN 4 YOUNG MALE PATIENTS HARBORING MUTATIONS IN THE AMH GENE : HORMONAL EVIDENCE OF NORMAL LEYDIG AND SERTOLI CELL COMPLEMENTS

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR12-Reproductive Hormones: Vital Effects Evidenced In Human Cohorts & Experimental Models
Translational
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 12:00 PM
Room 102 (Moscone Center)
Karine Braun1, Irène Netchine2, Paula Borrego1, Hélène Bony-Trifunovic1, Corinne Fouveaut3, Chrystel Leroy3, Christine Grapin4, Yara Rhayem3, Catherine Dodé3 and Najiba Lahlou*3
1CHU d'Amiens, AMIENS, France, 2Hopital Trousseau-Université Pierre et Marie Curie, PARIS, France, 3Hopital Cochin-Université Paris-Descartes, PARIS, France, 4Hopital Robert-Debre-Université Paris-Diderot, PARIS, France
Context. The persistance of Mullerian duct syndrome (PMDS) is a rare condition, clinically expressed as cryptorchidism and inguinal hernias. Mutations in the anti-Mullerian hormone gene (AMH) account for nearly half of reported cases. Very scarse data are available regarding testis function in the affected subjects.

Subjects. We have encountered 3 novel mutations, together with already known ones, in 4 infants operated on for inguinal hernia and bilateral cryptorchidism. Mullerian remnants were discovered during surgery and were not removed in order to preserve testis vascularization. Histological examination of testes on tissue samples collected during surgery showed seminiferous tubules containing germ cells. One boy, born from consanguineous parents, harbored the homozygous mutation p.W121X, c.363G>A. Three unrelated patients had the following genotypes: p.G74W / p.R302Q; p.Y167C / c.343-344delCT and p.E382X / p.E382X, respectively.

Methods. FSH and LH were measured by means of time resolved fluoroimmunoassay on Wallac Delfia autoanalyzer (PerkinElmer, Courtaboeuf, France). Testosterone was measured by mass spectrometry on Quattro Premier equipment (Waters, Saint-Quentin en Yvelines, France). Insulin-like peptide 3 (INSL3) was measured by fluoroimmunoassay (Phoenix reagents, Burlingame CA), inhibin B (INHB) and AMH by means of chemiluminescence immunoassay (Anshlabs reagents, Webster TX). Assays were performed on samples collected before and / or after surgery in these 4 infants.

Results. In all boys AMH was undetectable. FSH and LH, testosterone, INSL3 and INHB levels were within normal ranges for age. Gonadotropins and testis hormones exhibited the normal minipubertal postnatal changes, with higher levels of FSH (1.4-2.6 IU/L), LH (2.58-3.17 IU/L), testosterone (2.47-2.6 nmol/L), INSL3 (68-96 pg/ml) and inhibin B 187-221 pg/ml) at 3-5 months of age than afterwards (0.08-0.44 IU/L, 0.04-0.54 IU/L, 0.04-0.45 nmol/l, 38-40 pg/ml, and 110-117 pg/ml, respectively).

Conclusion. These data give evidence of normal pituitary-testis function in infants with PMDS despite cryptorchidism and surgical manipulation. Given the uncertainty regarding fertility of  adult males harboring a mutation in the AMH gene, a prolonged and close follow up of such patients should likely be beneficial to assess their gonadal prognosis.

Nothing to Disclose: KB, IN, PB, HB, CF, CL, CG, YR, CD, NL

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