• PMID: 19361789
• Gene Name: AR
• Condition: Male infertility, Sertoli-cell-only
• Association: Associated
• Mutation: 212A-->G in the CAG repeat, Q-->R
• Population size: 21
• Population details: 21 adult infertile men
• Sex: Male
• Infertility type: Male infertility
• Associated genes: AR
• Other associated phenotypes: Male infertility

A novel sequence variation in the transactivation regulating domain of the human androgen receptor

Hose KA, Häffner K, Fietz D, Gromoll J, Eckert T, Kliesch S, Siebert HC, Bergmann M.

OBJECTIVE: To study a novel sequence variation within the androgen receptors' N-terminal CAG repeat region and possible resulting consequences for the receptors' three-dimensional (3D) protein structure. DESIGN: Controlled clinical study. SETTING: University research and andrology clinic. PATIENT(S): Twenty-one adult infertile men. INTERVENTION(S): Ultraviolet laser-assisted microdissection (PALM, Microlaser Technology AG, Bernried, Germany), cloning into pGEM-T vector (Promega, Madison, WI), automated sequencing (Gene Scan 3.7 ABI Prim, Applied Biosystems, Foster City, CA), and Assisted Model Building with Energy Refinement (AMBER). MAIN OUTCOME MEASURE(S): Determination of the sequence of the CAG repeat of the androgen receptor gene and analysis of the 3D protein structure. RESULTS(S): In one hypergonadotropic azoospermic patient with Sertoli-cell-only syndrome, we found a punctual sequence variation of 212A-->G in the CAG repeat resulting in a glutamine-arginine substitution, which leads to a moderate conformational change of the alpha-helix from 34 A in length and 16 A in diameter (without mutation) to a slightly longer helix (43 A) with a smaller diameter (15 A). CONCLUSION(S): Whether the novel 212A-->G exchange in the CAG repeat leading to a glutamine-->arginine substitution and a change in alpha-helix structure may causally be related to the Sertoli-cell-only phenotype of the patient remains to be elucidated. FAU - Hose, Katja Anette AU - Hose KA AD - Institute of Veterinary Anatomy, University of Giessen, Frankfurterstrasse 98, Giessen, Germany. FAU - Häffner, Kristina AU - Häffner K FAU - Fietz, Daniela AU - Fietz D FAU - Gromoll, Jörg AU - Gromoll J FAU - Eckert, Thomas AU - Eckert T FAU - Kliesch, Sabine AU - Kliesch S FAU - Siebert, Hans-Christian AU - Siebert HC