scholarly journals Male Fertility Is Compatible with an Arg840Cys Substitution in the AR in a Large Chinese Family Affected with Divergent Phenotypes of AR Insensitivity Syndrome

2002 ◽  
Vol 87 (1) ◽  
pp. 347-351 ◽  
Author(s):  
Jianhua Chu ◽  
Rongmei Zhang ◽  
Zhimin Zhao ◽  
Wei Zou ◽  
Yefei Han ◽  
...  
Keyword(s):  
Sexual Development ◽  
Male Fertility ◽  
Genetic Disorder ◽  
External Genitalia ◽  
Mutant Gene ◽  
Androgen Insensitivity Syndrome ◽  
The Other ◽  
Chinese Family ◽  
Normal Range ◽  
Androgen Insensitivity

Androgen insensitivity syndrome (AIS) is a disorder of male sexual development caused by an absent or dysfunctional AR. Fertile cases with mild AIS and slightly impaired AR activity had been reported in literature, and their external genitalia were documented to be usually normal or subnormal. We reported here an Arg840Cys substitution in the AR gene in a large Chinese pedigree affected with AIS. The mutant gene may result in infertility for some affected males with or without hypospadias. However, it was also observed that the mutation did not affect the fertility of the other patients. The gonadotropin levels for one of these patients were within the normal range. Thus, whether normal levels of the gonadotropins are necessary for the preserved fertility of patients affected with this genetic disorder remains to be elucidated.

scholarly journals Different Clinical Presentations and Management in Complete Androgen Insensitivity Syndrome (CAIS)

2019 ◽  
Vol 16 (7) ◽  
pp. 1268 ◽  
Author(s):  
Lucia Lanciotti ◽  
Marta Cofini ◽  
Alberto Leonardi ◽  
Mirko Bertozzi ◽  
Laura Penta ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Androgen Insensitivity Syndrome ◽  
Childhood And Adolescence ◽  
Testicular Germ Cell Tumour ◽  
Unique Challenge ◽  
Complete Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity ◽  
Prognostic Features ◽  
Clinical Presentations ◽  
Increased Risk

Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive genetic disorder resulting from maternally inherited or de novo mutations involving the androgen receptor gene, situated in the Xq11-q12 region. The diagnosis is based on the presence of female external genitalia in a 46, XY human individual, with normally developed but undescended testes and complete unresponsiveness of target tissues to androgens. Subsequently, pelvic ultrasound or magnetic resonance imaging (MRI) could be helpful in confirming the absence of Mullerian structures, revealing the presence of a blind-ending vagina and identifying testes. CAIS management still represents a unique challenge throughout childhood and adolescence, particularly regarding timing of gonadectomy, type of hormonal therapy, and psychological concerns. Indeed this condition is associated with an increased risk of testicular germ cell tumour (TGCT), although TGCT results less frequently than in other disorders of sex development (DSD). Furthermore, the majority of detected tumoral lesions are non-invasive and with a low probability of progression into aggressive forms. Therefore, histological, epidemiological, and prognostic features of testicular cancer in CAIS allow postponing of the gonadectomy until after pubertal age in order to guarantee the initial spontaneous pubertal development and avoid the necessity of hormonal replacement therapy (HRT) induction. However, HRT is necessary after gonadectomy in order to prevent symptoms of hypoestrogenism and to maintain secondary sexual features. This article presents differential clinical presentations and management in patients with CAIS to emphasize the continued importance of standardizing the clinical and surgical approach to this disorder.

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.

scholarly journals Surface Rendering of External Genitalia of a Fetus at the 32nd Week of Gestation Affected by Partial Androgen Insensitivity Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Vincenzo Mazza ◽  
Emma Bertucci ◽  
Silvia Latella ◽  
Carlotta Cani ◽  
Pierluca Ceccarelli ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
External Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
Surface Rendering ◽  
Sry Gene ◽  
Androgen Insensitivity ◽  
4D Ultrasound ◽  
Genital Ambiguity ◽  
Parental Counseling ◽  
Partial Androgen Insensitivity Syndrome

Objectives. To demonstrate the feasibility of the prenatal diagnosis of partial androgen insensitivity syndrome by 3D-4D ultrasound.Methods. To report prenatal diagnosis of partial androgen insensitivity syndrome at 32nd week of gestation by 3D-4D ultrasound in a fetus with a 46XY karyotype, testing negative to the mutation analysis of SRY gene and the 5α-reductase 2 gene (SRD5A2).Results. 3D-4D surface rendering allows the detection of external and internal genital malformations and can address the prenatal diagnosis of PAIS and can exclude associated complications.Conclusions. Prenatal diagnosis of PAIS allows an adequate parental counseling and an early optimal management of the condition, not only for the psychological and social reflections but also for the avoidance of complications and postnatal morbidity due to misdiagnosis or delays in the treatment of the genital ambiguity.

The subcellular defects in the androgen insensitivity syndrome

1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S396-S402
Author(s):  
W. SWOBODA ◽  
K. HERKNER
Keyword(s):  
Binding Capacity ◽  
Kinetic Method ◽  
External Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
Normal Female ◽  
Androgen Insensitivity ◽  
Wide Range ◽  
Group A ◽  
Group B ◽  
Tissue Specimens

ABSTRACT The androgen insensitivity syndrome (AIS) was studied with consideration of the complexity of mechanisms involved on the intracellular level: testosterone (T) and dihydrotestosterone (DHT) receptors and the androgen-5α-reductase (A5R). Five children with "normal" female external genitalia (group A) and three patients with variable forms of ambiguity (group B), ages 1 to 18 years, were studied. Tissue specimens from genital skin were analysed for the Kd- and Nmaxvalues of the cytosolic and nuclear T- and DHT-receptors, as well as for the Km- and Vmax-data of the tissue specific A5R. The enzyme analyses were performed with a kinetic method. Results show that patients from group A mainly lack action of the nuclear DHT receptor, combined with reduces binding capacity in the cytosol. T binding was poor in both, cytosolic and nuclear fractions, respectively. Results of group B proved to be more inhomogenous, ranging from total absence of a DHT receptor to normal binding capacities in the nuclear fractions, accompanied by decreased cytosolic Nmax values for that ligand. T binding was poor in all patients of group B in the cytosolic and nuclear fractions, respectively. A5R was qualitatively normal in all patients examined, except one, but decreased enzyme activities could be observed in a wide range. In summary, the study confirms the complex mechanisms, presenting as AIS clinically. Moreover a close relationship between abnormalities of androgen receptor function and changes in A5R activity could be evaluated, thus confirming the recent theories about intracellular androgen action.

Complete androgen insensitivity syndrome: report of a case with solitary pelvic kidney

2006 ◽  
Vol 47 (2) ◽  
pp. 222-225 ◽  
Author(s):  
H. Tokgoz ◽  
O. Turksoy ◽  
S. Boyacigil ◽  
B. Sakman ◽  
E. Yuksel
Keyword(s):  
External Genitalia ◽  
Solitary Kidney ◽  
Pubic Hair ◽  
Androgen Insensitivity Syndrome ◽  
Primary Amenorrhea ◽  
Testicular Feminization ◽  
Unilateral Renal Agenesis ◽  
Complete Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity ◽  
Contralateral Kidney

Complete androgen insensitivity syndrome, commonly known as the testicular feminization syndrome, is characterized by a 46, XY karyotype, bilateral testes, absent or hypoplastic Wolffian ducts, and female-appearing external genitalia with diminished axillary and pubic hair development. Although initial diagnosis in the child is difficult, the syndrome must be suspected after puberty if primary amenorrhea is present. Coexistence of genital defects with urologic abnormalities is expected in these cases because of close embryologic origin. However, unilateral renal agenesis with pelvic ectopia of the contralateral kidney does not seem so common. We report a case of testicular feminization syndrome with a solitary kidney located in bony pelvis on the left side.

scholarly journals Ligand induced dissociation of the AR homodimer precedes AR monomer translocation to the nucleus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ryota Shizu ◽  
Kosuke Yokobori ◽  
Lalith Perera ◽  
Lee Pedersen ◽  
Masahiko Negishi
Keyword(s):  
Sexual Development ◽  
Hormone Receptors ◽  
Nuclear Translocation ◽  
Steroid Hormone ◽  
Binding Pocket ◽  
Androgen Insensitivity Syndrome ◽  
Steroid Hormone Receptors ◽  
Wild Type ◽  
Dimer Interface ◽  
Androgen Insensitivity

Abstract The androgen receptor (AR) regulates male sexual development. We have now investigated AR homodimerization, hormone-dependent monomerization and nuclear translocation in PC-3 and COS-1 cells, by utilizing mutations associated with the androgen insensitivity syndrome: Pro767Ala, Phe765Leu, Met743Val and Trp742Arg. AR wild type (WT) was expressed as a homodimer in the cytoplasm, while none of these mutants formed homodimers. Unlike AR WT which responded to 1 nM dihydrotestosterone (DHT) to dissociate and translocate into the nucleus, AR Pro767Ala and Phe765Leu mutants remain as the monomer in the cytoplasm. In the crystal structure of the AR LBD homodimer, Pro767 and Phe765 reside closely on a loop that constitutes the dimer interface; their sidechains interact with the Pro767 of the other monomer and with the DHT molecule in the ligand-binding pocket. These observations place Phe765 at a position to facilitate DHT binding to Pro767 and lead to dissociation of the AR homodimer in the cytoplasm. This Pro-Phe Met relay may constitute a structural switch that mediates androgen signaling and is conserved in other steroid hormone receptors.

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