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Androgen insensitivity syndrome AIS is an intersex condition that results in the partial or complete inability of the cell to respond to androgens. AIS is divided into three categories that are differentiated by жмите сюда degree of genital masculinization: Management of AIS is currently limited to symptomatic management ; no method is currently available to correct the malfunctioning androgen receptor proteins produced by AR gene mutations. Areas of management include sex assignmentgenitoplastygonadectomy in relation to tumor risk, hormone replacement therapygenetic counselingand psychological counseling.

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Androgen insensitivity syndrome AIS is an intersex condition that results in the partial or complete inability of the cell to respond to androgens. AIS is divided into three categories that are differentiated by the degree of genital masculinization: Management of AIS is currently limited to symptomatic management ; no method is currently available to correct the malfunctioning androgen receptor proteins produced by AR gene mutations. Areas of management include sex assignment , genitoplasty , gonadectomy in relation to tumor risk, hormone replacement therapy , genetic counseling , and psychological counseling.

The human androgen receptor AR is a protein encoded by a gene located on the proximal long arm of the X chromosome locus XqXq The AR gene contains two polymorphic trinucleotide microsatellites in exon 1. As of , over AR mutations have been reported in the AR mutation database, and the number continues to grow. Several case studies of fertile 46,XY males with AIS have been published, [4] [56] [57] [58] [59] although this group is thought to be a minority.

A genetic female conceived in such a way would receive her father's X chromosome, thus would become a carrier. A mutation in one but not both results in a minimally affected, fertile, female carrier. If the affected child is a genetic female, she, too, will be a carrier. A genetic female with mutations in both AR genes could theoretically result from the union of a fertile man with AIS and a female carrier of the gene, or from de novo mutation. However, given the scarcity of fertile AIS men and low incidence of AR mutation, the chances of this occurrence are small.

The phenotype of such an individual is a matter of speculation; as of , no such documented case has been published. Individuals with partial AIS, unlike those with the complete or mild forms, present at birth with ambiguous genitalia , and the decision to raise the child as male or female is often not obvious. The effects that androgens have on the human body virilization , masculinization, anabolism , etc. The following series of steps illustrates how androgens and the androgen receptor work together to produce androgenic effects: In this way, androgens bound to androgen receptors regulate the expression of target genes, thus produce androgenic effects.

Theoretically, certain mutant androgen receptors can function without androgens; in vitro studies have demonstrated that a mutant androgen receptor protein can induce transcription in the absence of androgen if its steroid binding domain is deleted. Human embryos develop similarly for the first six weeks, regardless of genetic sex 46,XX or 46,XY karyotype ; the only way to tell the difference between 46,XX or 46,XY embryos during this time period is to look for Barr bodies or a Y chromosome.

By the fifth week, the genital ridges differentiate into an outer cortex and an inner medulla , and are called indifferent gonads. Until around the seventh week of development, the embryo has indifferent sex accessory ducts , which consist of two pairs of ducts: Masculinization of the male external genitalia the penis , penile urethra , and scrotum , as well as the prostate , are dependent on the androgen dihydrotestosterone.

Mutations in the androgen receptor gene can cause problems with any of the steps involved in androgenization, from the synthesis of the androgen receptor protein itself, through the transcriptional ability of the dimerized , androgen-AR complex. This predictive ability is primarily retrospective in origin; the different functional domains of the AR gene have been elucidated by analyzing the effects of specific mutations in different regions of the AR.

Some mutations can adversely impact more than one functional domain. For example, a mutation in one functional domain can have deleterious effects on another by altering the way in which the domains interact. Other, more complex relationships have been observed as a consequence of mutated AR ; some mutations associated with male phenotypes have been linked to male breast cancer , prostate cancer , or in the case of spinal and bulbar muscular atrophy , disease of the central nervous system.

The trinucleotide repeat expansion of the polyglutamine tract of the AR gene that is associated with SBMA results in the synthesis of a misfolded AR protein that the cell fails to proteolyze and disperse properly.

The phenotypes that result from the insensitivity to androgens are not unique to AIS, thus the diagnosis of AIS requires thorough exclusion of other causes. Each of the three types of AIS complete, partial, and mild has a different list of differential diagnoses to consider. AIS is broken down into three classes based on phenotype: Quigley et al. Estimates for the incidence of androgen insensitivity syndrome are based on a relatively small population size, thus are known to be imprecise.

Preimplantation genetic diagnosis PGD or PIGD refers to genetic profiling of embryos prior to implantation as a form of embryo profiling , and sometimes even of oocytes prior to fertilization. When used to screen for a specific genetic sequence, its main advantage is that it avoids selective pregnancy termination, as the method makes it highly likely that a selected embryo will be free of the condition under consideration.

Recorded descriptions of the effects of AIS date back hundreds of years, although significant understanding of its underlying histopathology did not occur until the s. The first descriptions of the effects of AIS appeared in the medical literature as individual case reports or as part of a comprehensive description of intersex physicalities.

In , Scottish obstetrician Sir James Young Simpson published one such description [] in an exhaustive study of intersexuality that has been credited with advancing the medical community's understanding of the subject. An alternative system of nomenclature has been recently suggested, [] but the subject of exactly which word or words should be used in its place still one of much debate.

For example, 46,XY individuals who have a female phenotype, but also have testes instead of ovaries — a group that includes all individuals with CAIS, as well as some individuals with PAIS — are classified as having "male pseudohermaphroditism", while individuals with both an ovary and a testis or at least one ovotestis are classified as having " true hermaphroditism ".

Previous definitions of "pseudohermaphroditism" relied on perceived inconsistencies between the internal and external organs; the "true" sex of an individual was determined by the internal organs, and the external organs determined the "perceived" sex of an individual.

German-Swiss pathologist Edwin Klebs is sometimes noted for using the word "pseudohermaphroditism" in his taxonomy of intersexuality in , [] although the word is clearly not his invention as is sometimes reported; the history of the word " pseudohermaphrodite " and the corresponding desire to separate "true" hermaphrodites from "false", "spurious", or "pseudo" hermaphrodites, dates back to at least , when Dutch anatomist Frederik Ruysch used it in a publication describing a subject with testes and a mostly female phenotype.

In , American gynecologist John Morris provided the first full description of what he called "testicular feminization syndrome" based on 82 cases compiled from the medical literature, including two of his own patients. A distinct name has been given to many of the various presentations of AIS, such as Reifenstein syndrome , [] Goldberg-Maxwell syndrome , [] Morris' syndrome , [] Gilbert-Dreyfus syndrome , [] Lub's syndrome , [] "incomplete testicular feminization" , [] Rosewater syndrome , [] and Aiman's syndrome Over the last 60 years, as reports of strikingly different phenotypes were reported to occur even among members of the same family, and as steady progress was made towards the understanding of the underlying molecular pathogenesis of AIS, these disorders were found to be different phenotypic expressions of one syndrome caused by molecular defects in the androgen receptor gene.

AIS is now the accepted terminology for the syndromes resulting from unresponsiveness of the target cell to the action of androgenic hormones. The more virilized phenotypes of AIS have sometimes been described as "undervirilized male syndrome", "infertile male syndrome", "undervirilized fertile male syndrome", etc. She has given interviews about her condition [] [] and founded "Girl Comet, a non-profit diversity awareness and inspiration initiative.

In , fashion model Hanne Gaby Odiele disclosed that she was born with the intersex trait androgen insensitivity syndrome. As a child, she underwent medical procedures relating to her condition , [] which she said took place without her or her parents' informed consent.

In the Japanese horror novel Ring , by Koji Suzuki later adapted into Japanese, Korean, and American films , the central antagonist Sadako has this syndrome. The character, Lauren Cooper, played by Bailey De Young , was the first intersex series regular on American television. Miami , the primary suspect has AIS which gets him off a rape charge.

She attends a cervical smear and brings up that she has never had a period, and is concerned about having children as she is about to be married. She is then diagnosed with "testicular feminisation syndrome", the old term for AIS. From Wikipedia, the free encyclopedia. Androgen insensitivity syndrome AIS results when the function of the androgen receptor AR is impaired. The AR protein pictured mediates the effects of androgens in the human body.

Specialty Endocrinology Androgen insensitivity syndrome AIS is an intersex condition that results in the partial or complete inability of the cell to respond to androgens. Main article: Androgen receptor. Androgen enters the cell. Only certain organs in the body, such as the gonads and the adrenal glands , produce the androgen testosterone. Testosterone is converted into dihydrotestosterone , a chemically similar androgen, in cells containing the enzyme 5-alpha reductase.

Both androgens exert their influence through binding with the androgen receptor. The androgen receptor is expressed ubiquitously throughout the tissues of the human body.

Before it binds with an androgen, the androgen receptor is bound to heat shock proteins. These heat shock proteins are released upon androgen binding. Androgen binding induces a stabilizing, conformational change in the androgen receptor. The two zinc fingers of the DNA-binding domain are exposed as a result of this new conformation. Receptor phosphorylation can occur before androgen binding, although the presence of androgen promotes hyperphosphorylation.

The biological ramifications of receptor phosphorylation are unknown. Nucleocytoplasmic transport is in part facilitated by an amino acid sequence on the AR called the nuclear localization signal. The AR's nuclear localization signal is primarily encoded in the hinge region of the AR gene. Dimerization is mediated by the second nearest the 3' end zinc finger. Target genes contain or are flanked by transcriptional enhancer nucleotide sequences that interact with the first zinc finger.

These areas are called androgen response elements. Type I coactivators i. Diagnosis of Complete Androgen Insensitivity Syndrome. Diagnosis of Partial Androgen Insensitivity Syndrome. Diagnosis of Mild Androgen Insensitivity Syndrome. Chromosomal anomalies: Frasier syndrome associated with progressive glomerulopathy Denys-Drash syndrome associated with nephropathy and Wilms tumor WAGR syndrome associated with Wilms tumor and aniridia McKusick-Kaufman syndrome associated with postaxial polydactyly Robinow syndrome associated with dwarfism Aarskog-Scott syndrome associated with facial anomalies Hand-foot-genital syndrome associated with limb malformations Popliteal pterygium syndrome associated with extensive webbing behind knees Kallmann syndrome often associated with anosmia Hypospadias not otherwise specified Cryptorchidism not otherwise specified vaginal atresia not otherwise specified.

Complete androgen insensitivity syndrome. Partial androgen insensitivity syndrome. Mild androgen insensitivity syndrome. Management of Complete Androgen Insensitivity Syndrome. Management of Partial Androgen Insensitivity Syndrome. Management of Mild Androgen Insensitivity Syndrome. Best Pract. Hormones Athens. Suppl 3: Ann Nucl Med. American Journal of Human Genetics. American Journal of Medical Genetics. April The androgen receptor gene mutations database".

Harrison's endocrinology.

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