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Updated: Jun 24, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
A novel sequence variation in the transactivation regulating domain of the human androgen receptor
Katja Anette Hose1, Kristina Häffner, Daniela Fietz
1Institute of Veterinary Anatomy, University of Giessen, Frankfurterstrasse 98, Giessen, Germany.
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.
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