Three novel AMH gene mutations in a patient with persistent mullerian duct syndrome and normal AMH serum dosage.

Background: Persistent mullerian duct syndrome (PMDS) is characterized by the presence of uterus, fallopian tubes and the upper part of the vagina in 46,XY patients with perfectly virilized external genitalia. It is mostly caused by mutations of the AMH or AMH type 2 receptor (AMHR2) gene. The AMH serum level is very often low or undetectable in the AMH gene defect and normal in the AMHR2 gene defect. Aim: We investigate an Italian patient, genotypically and phenotypically male, observed at 1 month of age for a right inguinal hernia that at surgery showed the presence of both testes in the same hernial sac and uterus and fallopian tubes in the abdomen. Results: Genetic tests first showed the absence of the common 27-bp deletion in the AMHR2 gene, then the presence of three new sequence variations in the AMH gene leading to the following variants: the p.A405P carried by the paternal allele; the p.G326V plus the p.V508A carried by the maternal allele. Conclusions: The determination of serum AMH, performed after the genetic analysis, showed a normal level for age, suggesting that these mutations may affect the function and the bioactivity of the hormone and not the secretion rate. Copyright (C) 2008 S. Karger AG, Basel.