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


METHODS
Controlled clinical study.


METHODS
University research and andrology clinic.


METHODS
Twenty-one adult infertile men.


METHODS
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).


METHODS
Determination of the sequence of the CAG repeat of the androgen receptor gene and analysis of the 3D protein structure.


RESULTS
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).


CONCLUSIONS
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.
Hose
Katja Anette
KA
Institute of Veterinary Anatomy, University of Giessen, Frankfurterstrasse 98, Giessen, Germany.
Häffner
Kristina
K
Fietz
Daniela
D
Gromoll
Jörg
J
Eckert
Thomas
T
Kliesch
Sabine
S
Siebert
Hans-Christian
HC
Bergmann
Martin
M
D019943:Amino Acid Substitution; D001120:Arginine; D053713:Azoospermia / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D014644:Genetic Variation; D005973:Glutamine; D006801:Humans; D007621:Karyotyping; D008297:Male; D011487:Protein Conformation; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics*; D017384:Sequence Deletion; D012708:Sertoli Cells / Q000473:pathology; D018911:Trinucleotide Repeats; D055815:Young Adult
D011944:Receptors, Androgen; D005973:Glutamine; D001120:Arginine