A Novel Point Mutation in the Hormone Binding Domain of the Androgen Receptor Associated with Partial and Minimal Androgen Insensitivity Syndrome

2003 ◽  
Vol 16 (2) ◽  
Author(s):  
A. Galli-Tsinopoulou ◽  
O. Hiort ◽  
T. Schuster ◽  
G. Messer ◽  
U. Kuhnle
Keyword(s):  
Androgen Receptor ◽  
Point Mutation ◽  
Androgen Insensitivity Syndrome ◽  
Binding Domain ◽  
Hormone Binding ◽  
Androgen Insensitivity ◽  
Hormone Binding Domain

Single amino acid substitution (840Arg → His) in the hormone-binding domain of the androgen receptor leads to incomplete androgen insensitivity syndrome associated with a thermolabile androgen receptor

1994 ◽  
Vol 130 (6) ◽  
pp. 569-574 ◽  
Author(s):  
Kyosuke Imasaki ◽  
Tomonobu Hasegawa ◽  
Taijiro Okabe ◽  
Yoshiyuki Sakai ◽  
Masafumi Haji ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Androgen Insensitivity Syndrome ◽  
Binding Domain ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
Hormone Binding ◽  
Androgen Insensitivity ◽  
Hormone Binding Domain

Imasaki K, Hasegawa T. Okabe T. Sakai Y. Haji M. Takayanagi R, Nawata H. Single amino acid substitution (840Arg → His) in the hormone-binding domain of the androgen receptor leads to incomplete androgen insensitivity syndrome associated with a thermolabile androgen receptor. Eur I Endocrinol 1994;130:569–74. ISSN 0804–4643 We have characterized the androgen receptor in a Japanese girl and her maternal cousin in a family with incomplete androgen insensitivity syndrome, and have investigated the molecular basis. Wholecell androgen binding assay in cultured genital skin fibroblasts from both patients showed a normal maximum binding capacity and a normal apparent dissociation constant. However, androgen binding in fibroblasts from both patients decreased to 30% when the assay temperature was raised from 30°C to 41°C, indicating the presence of the thermolability of ligand binding to the androgen receptor. Sequence analysis of the coding exons of the androgen receptor gene from the patients revealed a single nucleotide substitution at position 2881 in exon G, resulting in the conversion of arginine (CGT) to histidine (CAT) at amino acid position 840 in the hormone-binding domain of the androgen receptor. The family study showed that the mothers and the maternal grandmother of the patients are heterozygous carriers for this mutation, whereas the father does not carry it, supporting the view that androgen insensitivity syndrome is an X chromosome-linked disorder. The single amino acid substitution may explain the qualitative abnormality of the androgen receptor displaying thermolability, which is thought to be the pathogenesis of incomplete androgen insensitivity syndrome in the patients. Kyosuke Imasaki, Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan

Androgen Insensitivity Syndrome in a Family of Warmblood Horses Caused by a 25-bp Deletion of the DNA-Binding Domain of the Androgen Receptor Gene

2017 ◽  
Vol 11 (1) ◽  
pp. 40-45 ◽  
Author(s):  
G. Eastman Welsford ◽  
Rikke Munk ◽  
Daniel A.F. Villagómez ◽  
Poul Hyttel ◽  
W. Allan King ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Dna Binding ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Androgen Insensitivity Syndrome ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Androgen Insensitivity

Single nucleotide substitution of the androgen receptor gene in a case with receptor-positive androgen insensitivity syndrome (complete form)

1993 ◽  
Vol 128 (4) ◽  
pp. 355-360 ◽  
Author(s):  
Hiroyuki Kasumi ◽  
Shinji Komori ◽  
Noriyuki Yamasaki ◽  
Hiroki Shima ◽  
Shinzo Isojima
Keyword(s):  
Androgen Receptor ◽  
Genetic Disorders ◽  
Genetic Disorder ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Androgen Insensitivity Syndrome ◽  
Single Nucleotide ◽  
Androgen Insensitivity ◽  
Complete Form ◽  
Hormone Binding Domain

Complete androgen insensitivity syndrome is caused by X chromosome linked disorder resulting in a target organ insensitivity to androgen. Two variants have been described in this syndrome. In the first, the binding of [3H] dihydrotestosterone(17β-hydroxy-5α-androstan-3-one) to the androgen receptor is undetectable (receptor-negative), whereas in the second variant normal levels of androgen receptor are detectable but the binding of [3H] dihydrotesterone to the androgen receptor is significantly thermolabile under certain conditions (receptor-positive). In receptor-negative cases, genetic disorders of the androgen receptor gene have been demonstrated. On the other hand, the genetic disorder of androgen receptor in receptor-positive cases is little known. In this study, the gene structure of androgen receptor in a receptor-positive case using a polymerase chain reaction technique is studied in the fibroblasts cultured from genital skin. The results demonstrate that the substitution of nucleotide (guanine→cytosine) in exon G of the androgen receptor causes the replacement of an amino acid in position 820 (glycine→alanine) which occurs in the hormone-binding domain of the androgen receptor. The substitution of nucleotide may explain the thermolability of the androgen receptor in a case with receptor-positive androgen insensitivity syndrome.

Agonists, but not antagonists, alter the conformation of the hormone-binding domain of androgen receptor.

Endocrinology ◽  
1994 ◽  
Vol 134 (2) ◽  
pp. 998-1001 ◽  
Author(s):  
P J Kallio ◽  
O A Jänne ◽  
J J Palvimo
Keyword(s):  
Androgen Receptor ◽  
Binding Domain ◽  
Hormone Binding ◽  
Hormone Binding Domain
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