scholarly journals The Worldwide Landscape of Variants in the Androgen Receptor Gene Related to Androgen Insensitivity Syndrome: An Integrative Analysis

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A511-A512
Author(s):  
Rafael Loch Batista ◽  
Berenice Bilharinho Mendonca
Keyword(s):  
Receptor Gene ◽  
In Silico Analysis ◽  
External Genitalia ◽  
Androgen Receptor Gene ◽  
Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity ◽  
Functional Studies ◽  
Phenotype Variability ◽  
Large Deletions ◽  
Sex Assignment

Abstract Androgen Insensitivity Syndrome (AIS) is an X-linked genetic disease and it is the most common cause of 46,XY DSD. It is divided into 3 phenotypes: complete (CAIS), partial (PAIS), and mild (MAIS). To analyse the landscape of AR variants in AIS we collected all AR variants reported among AIS in the literature (Pubmed, EMBASE, Medline) and websites (ensemble, HGMD, ClinVar). They were analyzed according to phenotype, exon location, domain, amino acid (aa) conservation, sex assignment, external genitalia virilization (EMS score), molecular and functional studies. Conservation analysis of the AR were performed using CONSURF plataform. To test our hypothesis that non-synonymous AR variants could also impact on splicing, we used both ESEfinder and Human Splicing Finder 3.1. We founded 901 individuals with AIS: CAIS = 565 (62.7%); PAIS = 282 (31.3%); and MAIS = 54 (6%). They had 465 different AR variants: CAIS = 290 (62.3%); PAIS = 135 (29.1%); and MAIS = 40 (8.6%). Among MAIS and PAIS, most variants were at LDB domain (22 out 40 = 55% and 84 out 135 = 62.2%, respectively) whereas they were at NTD domain among CAIS (129 out 290 = 44.5%). Most were missense (81%). However, small indels (11%), nonsense (3%), splicing sites (4%) and large deletions (1%) were all reported. Non-synonymous AR variants accounting for 60%, 96%, and 100% of CAIS, PAIS, and MAIS, respectively. Synonymous AR variants were rarely found (n=3). In 81% only the AR sequencing was performed. The remaining was detected by WES (18%) or WGS (1%). Deep intronic variant was detected in PAIS (n=1) while variants in the 5’UTR of the AR gene in both PAIS and CAIS (n=2). Most AR variants were located at conserved aa (78%), but AR variants at non-conserved aa were more frequently indels (p<.01). Functional studies were found in 38%, mostly showing reduced AR expression. Among PAIS, 48% (n=134) were assigned as male at birth. The median EMS was 5 (95% CI, 5-7) in those assigned as male while it was 3.2 (95% CI, 2-6) in those assigned as female (p<.01). The median of EMS score was lower in variants at NTD domain (2.8, 95% CI, 0-7). We identified 34 AR variants causing more than one AIS phenotype (mostly CAIS and PAIS) and 6 AR variants causing all of three AIS phenotypes. In silico analysis suggests potential to disrupt normal AR splicing in 18 (53%) by creating new acceptor or donor splicing sites (n=11) or exonic splicing signals (n=7). More severe AR variants are related to CAIS. Most AR variants were reported only based on AR sequencing. Therefore, the functional pathogenicity of these variants remains unclear. Further studies including WGS could help to expand the molecular diagnosis of AIS. There is phenotype variability in AIS. So, sex assignment of patients with PAIS cannot be based on a specific identified AR gene mutation. There is potential to alter splicing among non-synonymous AR variants, which could be an explanation for phenotype variability in AIS.

Laparoscopic Repositioning of Gonads from the Labia Majora or Inguinal Canal into the Abdominal Cavity in Pediatric Complete Androgen Insensitivity Syndrome Patients with Inguinal Hernia

2021 ◽  
pp. 1-7
Author(s):  
Sung Ryul Lee
Keyword(s):  
Inguinal Hernia ◽  
Pediatric Patients ◽  
Inguinal Canal ◽  
Receptor Gene ◽  
Abdominal Cavity ◽  
External Genitalia ◽  
Androgen Receptor Gene ◽  
Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity ◽  
Labia Majora

Androgen insensitivity syndrome (AIS) is a congenital condition characterized by a 46,XY karyotype but with a female phenotype caused by mutations in the androgen receptor gene located on the X chromosome. In patients with complete AIS (CAIS), preservation of the gonad is recommended until puberty, and gonadectomy can be regarded subsequently. The location of the gonads should be considered, because positions in the labia majora or inguinal canals can cause discomfort. Here, the laparoscopic reposition of gonads into the abdominal cavity in pediatric patients with CAIS is reported. From 2013 to 2019, laparoscopic inguinal hernia repair was performed in 2,061 pediatric patients with inguinal hernias aged <10 years and with female external genitalia. Among them, 11 had CAIS. Gonads located in the labia majora or inguinal canal were repositioned into the abdominal cavity. The mean age was 18.9 months (range 1–110 months). The gonads were located in the inguinal canal in 7 patients, in the labia majora in 3, and in the abdominal cavity in 1. Laparoscopic repositioning of such gonads into the abdominal cavity is feasible in pediatric patients with an inguinal hernia and CAIS.

La sindrome di Morris

2009 ◽  
pp. 93-105
Author(s):  
Chiara Simonelli ◽  
Veronica Vizzari ◽  
Alessandra Perilli
Keyword(s):  
Receptor Gene ◽  
External Genitalia ◽  
Androgen Receptor Gene ◽  
Androgen Insensitivity Syndrome ◽  
Gender Assignment ◽  
Minimal Impact ◽  
Androgen Insensitivity ◽  
Precise Diagnosis ◽  
Female External Genitalia ◽  
Terapia Ormonale

The Morris syndrome. Androgen insensitivity syndrome (AIS) is a genetic disease caused by mutations in the androgen receptor gene. AIS patients are individuals with a 46, XY karyotype. The phenotype consists in female external genitalia, short vagina, absent mullerian structures, and abdominal, inguinal or intralabial primordial testes. Precise diagnosis, that differentiating between complete (CAIS) and partial (PAIS) form, requires clinical and hormonal investigation and is of great importance for appropriate gender assignment. The CAIS has a minimal impact of one in 99,000 births, for the PAIS, however, there aren't some statistics available, but generally it should be with a lower impact, approximately ten times less than CAIS.Key words: Morris syndrome, androgen insensitivity syndrome, CAIS, PAIS, gonadectomy, hormonal replacement therapy, vaginal ipoplasia.Parole chiave: sindrome di Morris, sindrome da insensibilitŕ agli androgeni, CAIS, PAIS, gonadectomia, terapia ormonale sostitutiva, ipoplasia vaginale.

scholarly journals A Novel Mutation of the AR Androgen Receptor Gene

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A694-A694
Author(s):  
Abdullah Abdulruhman Aljasser
Keyword(s):  
Androgen Receptor ◽  
Novel Mutation ◽  
Receptor Gene ◽  
External Genitalia ◽  
Androgen Receptor Gene ◽  
Androgen Insensitivity Syndrome ◽  
Loss Of Function ◽  
Androgen Insensitivity ◽  
Androgen Synthesis ◽  
Voice Changes

Abstract Androgen insensitivity syndrome (AIS), formerly known as testicular feminization, is an X-linked recessive condition resulting in a failure of normal masculinization of the external genitalia in chromosomally male individuals. The basic etiology of androgen insensitivity syndrome is a loss-of-function mutation in the androgen receptor (AR) gene. Loss of AR function means that, despite normal levels of androgen synthesis, the typical postreceptor events that mediate the effects of hormones on tissues do not occur. This results in the phenotype of prenatal undervirilization of external genitalia, absence of pubic and axillary hair, lack of acne, and absence of voice changes at puberty We present This baby reffered at age of 2 months from pediatric surgery as a case of bilateral inguinal hernia and chromosomes 46xy. Phenotypically female no male structures no phallus and single opening and visible labia, both test are in the inguinal canals. HCG stimulation test shows: Testosterone: the level at (0) time: 0.8 nmol/l then 3 days: 31.4 nmol/l. DHT dihydrotetostrerone: the level at (0) time: 13 NG/L then 3 days: 485 The baby was given 3 doses of Testosterone injections 150mg but no response at the genetalia. Radiological investigations shows ultrasound both tests at the inguinal canals and no uterus Also MRI of pelvis shows absence of uterus and both test at the inguinal canals Molecular genetics analysis for Androgen receptor gene: Exon 7 c.2512 G &gt;A hem. P.Glu838lys missense, novel VUS,likely pathogenic. The segregations analysis test in the process. Her we present a novel mutation of the AR gene not reported yet in literature.

scholarly journals Complete Androgen Insensitivity Syndrome: From Bench to Bed

2021 ◽  
Vol 22 (3) ◽  
pp. 1264
Author(s):  
Nina Tyutyusheva ◽  
Ilaria Mancini ◽  
Giampiero Igli Baroncelli ◽  
Sofia D’Elios ◽  
Diego Peroni ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Hormone Replacement ◽  
Basic Research ◽  
Well Being ◽  
Androgen Receptor Gene ◽  
Androgen Insensitivity Syndrome ◽  
Primary Amenorrhea ◽  
Complete Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity

Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (AR). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the AR gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS.

Prenatal prediction of androgen insensitivity syndrome using exon 1 polymorphism of the androgen receptor gene

1992 ◽  
Vol 43 (7) ◽  
pp. 659-663 ◽  
Author(s):  
Jean Marc Lobaccaro ◽  
Serge Lumbroso ◽  
Françoise Carré Pigeon ◽  
Jean-Louis Chaussain ◽  
Jean-Edmond Toublanc ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity ◽  
Exon 1

scholarly journals Partial androgen insensitivity syndrome presenting as pubertal gynecomastia: clinical and hormonal findings and a novel mutation in the androgen receptor gene

2018 ◽  
Vol 2018 ◽  
Author(s):  
Priya Vaidyanathan ◽  
Paul Kaplowitz
Keyword(s):  
Androgen Receptor ◽  
Novel Mutation ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Androgen Insensitivity Syndrome ◽  
List Type ◽  
Androgen Insensitivity ◽  
Estrogen Production ◽  
Partial Androgen Insensitivity Syndrome ◽  
Pubertal Gynecomastia

Summary Pubertal gynecomastia is common, can be seen in 65% of the adolescent boys and is considered physiological. It is thought to be due to transient imbalance between the ratio of testosterone and estradiol in the early stages of puberty. It resolves in 1–2 years and requires no treatment. However, more persistent and severe pubertal gynecomastia is less common and can be associated with pathological disorders. These can be due to diminished androgen production, increased estrogen production or androgen resistance. We report a case of persistent pubertal gynecomastia due to partial androgen insensitivity syndrome (PAIS), classical hormone findings and a novel mutation in the androgen receptor (AR) gene. Learning points: Laboratory testing of follicle-stimulating hormone (FSH), leutinizing hormone (LH) and testosterone for pubertal gynecomastia is most helpful in the setting of undervirization. The hormonal finding of very high testosterone, elevated LH and estradiol and relatively normal FSH are classical findings of PAIS. Gynecomastia due to PAIS will not resolve and surgery for breast reduction should be recommended.

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