• PMID: 14673134
• Gene Name: AMH
• Condition: Persistent Mullerian duct syndrome
• Association: The addition of a cysteine in an N-terminal domain mutant, R194C, prevents proper folding, whereas the elimination of the cysteine involved in forming the interchain disulfide bond, in a C-terminal domain mutant, C525Y, leads to a truncation at the C term
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Persistent Mullerian duct syndrome

Mutations of the anti-mullerian hormone gene in patients with persistent mullerian duct syndrome: biosynthesis, secretion, and processing of the abnormal proteins and analysis using a three-dimensional model

Belville C, Van Vlijmen H, Ehrenfels C, Pepinsky B, Rezaie AR, Picard JY, Josso N, di Clemente N, Cate RL.

Anti-Müllerian hormone (AMH), a TGF-beta family member, determines whether an individual develops a uterus and Fallopian tubes. Mutations in the AMH gene lead to persistent Müllerian duct syndrome in males. The wild-type human AMH protein is synthesized as a disulfide-linked dimer of two identical 70-kDa polypeptides, which undergoes proteolytic processing to generate a 110-kDa N-terminal dimer and a bioactive 25-kDa TGF-beta-like C-terminal dimer. We have studied the biosynthesis and secretion of wild-type AMH and of seven persistent Müllerian duct syndrome proteins, containing mutations in either the N- or C-terminal domain. Mutant proteins lacking the C-terminal domain are secreted more rapidly than full-length AMH, whereas single amino acid changes in both domains can have profound effects on protein stability and folding. The addition of a cysteine in an N-terminal domain mutant, R194C, prevents proper folding, whereas the elimination of the cysteine involved in forming the interchain disulfide bond, in a C-terminal domain mutant, C525Y, leads to a truncation at the C terminus. A molecular model of the AMH C-terminal domain provides insights into how some mutations could affect biosynthesis and function. FAU - Belville, Corinne AU - Belville C AD - Unité de REcherches sur l'Endocrinologie du Développement (Institut National de la Santé et de la Recherche Médicale), Clamart, France. FAU - Van Vlijmen, Herman AU - Van Vlijmen H FAU - Ehrenfels, Christian AU - Ehrenfels C FAU - Pepinsky, Blake AU - Pepinsky B FAU - Rezaie, Alireza R AU - Rezaie AR FAU - Picard, Jean-Yves AU - Picard JY FAU - Josso, Nathalie AU - Josso N FAU - di Clemente, Nathalie AU - di Clemente N