PREMIOS de la Sociedad Latinoamericana de Endocrinología Pediátricia (SLEP) otorgados en el XXVI Congreso de la Sociedad Latinoamericana de Endocrinología Pediátricia, Buenos Aires, 2016.


Disruption in SF1-mediated AMH promoter regulation leading to Persistent Müllerian Duct Syndrome (PMDS). Valeri, C(1); di Clemente, N(2, 3); Marshall, I(4); Schteingart, H(1); Josso, N(2, 3); Rey, R(1, 5); Picard, J(2, 3)

Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez. C1425EFD Buenos Aires, Argentina (2) CNRS, UMR8251, Biologie Fonctionnelle et Adaptative, F-75013, Université Paris Diderot, Sorbonne Paris Cité. F-75013 Paris, France (3) INSERM U1133, Physiologie de l’Axe Gonadotrope, F-75013, Université Paris Diderot, Sorbonne Paris Cité. F-75013 Paris, France (4) Division of Pediatric Endocrinology, Rutgers-Robert Wood Johnson Medical School, Child Health Institute of New Jersey. New Brunswick, N J08901, USA (5) Departamento de Histología, Biología Celular, Embriología y Genética, Facultad de Medicina, Universidad de Buenos Aires. C1121ABG Buenos Aires, Argentina


In early fetal life, AMH secreted by the testes provokes the regression of Müllerian ducts. AMH expression in fetal Sertoli cells is triggered by SOX9, and further up regulated by SF1, GATA4 and WT1, all binding to specific sites on the proximal AMH gene promoter.

The absence of AMH signalling in the XY fetus results in the Persistent Müllerian duct syndrome (PMDS).

We report the case of a non-dysmorphic newborn who presented with a normal sized penis and non-palpable gonads. Lab work-up showed normal serum testosterone (358 ng/dl), very low serum AMH (7.8 pmol/l) and a 46,XY karyotype. A sonogram and MRI showed a uterus measuring 5 x 1.4 x 1.9 cm; VCUG showed a normal male urethra without a urogenital sinus.

DNA sequencing detected no mutations in the AMH gene coding sequences, but a homozygous single-base deletion (c.-225delA) was identified at a putative SF1 response element of the AMH promoter. The AMH promoter activity of the c.-225delA variant, analysed in luciferase assays, was decreased by 58 ± 14%, to a similar extent (66 ± 5%) of what was observed when the SF1 site was completely disrupted by in vitro directed mutagenesis. The interaction between SF1 and its binding site was lost when the oligonucleotide carried c.-225delA or the fully disrupted SF1 site, when studied by EMSA.

In conclusion, the single base deletion c.-225delA within the SF1 site of the AMH gene promoter impaired SF1 binding to andtransactivation of the AMH promoter, resulting in extremely decreased AMH production, leading to PMDS in this patient. This is the first description of an AMH promoter mutation leading to PMDS.

©2020 SLEP / Sociedad Latinoamericana de Endocrinología Pediatrica