Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 May;12(2):71-77.
doi: 10.5582/irdr.2023.01024.

Molecular genetics and general management of androgen insensitivity syndrome

Zhongzhong Chen  1   2   3 , Pin Li  4 , Yiqing Lyu  1 , Yaping Wang  1 , Kexin Gao  1 , Jing Wang  1 , Fuying Lan  1 , Fang Chen  1   2
Affiliations
Review

Molecular genetics and general management of androgen insensitivity syndrome

Zhongzhong Chen et al. Intractable Rare Dis Res. 2023 May.

Abstract

Androgen insensitivity syndrome (AIS) is a rare genetic disorder that affects the development of the male reproductive system in individuals with a 46,XY karyotype. In addition to physical impacts, patients with AIS may face psychological distress and social challenges related to gender identity and acceptance. The major molecular etiology of AIS results from hormone resistance caused by mutations in the X-linked androgen receptor (AR) gene. Depending on the severity of androgen resistance, the wide spectrum of AIS can be divided into complete AIS (CAIS), partial AIS (PAIS), or mild AIS (MAIS). Open issues in the treatment and management of AIS include decisions about reconstructive surgery, genetic counseling, gender assignment, timing of gonadectomy, fertility and physiological outcomes. Although new genomic approaches have improved understanding of the molecular causes of AIS, identification of individuals with AIS can be challenging, and molecular genetic diagnosis is often not achievable. The relationship between AIS genotype and phenotype is not well established. Therefore, the optimal management remains uncertain. The objective of this review is to outline the recent progress and promote understanding of AIS related to the clinical manifestation, molecular genetics and expert multidisciplinary approach, with an emphasis on genetic etiology.

Keywords: AIS; androgen receptor; disorders of sex development (DSD); genetics.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Structure and function of the androgen receptor (AR) gene, distribution of AR mutations in patients with AIS and androgen action. (A). A schematic representation of AR gene and AR protein. (B). Distribution of different types of AR mutations in AIS showed that mutations with larger effect size (stop codon, insertion, deletion and duplication) are more frequently reported in individuals with CAIS in the androgen receptor mutations database. The asterisks indicate significant excess of mutations with larger effect size (***p < 0.001). (C). Mechanism of AR activation through DHT binding.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Morris JM. The syndrome of testicular feminization in male pseudohermaphrodites. Am J Obstet Gynecol. 1953; 65:1192-1211. - PubMed
    1. Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J. Androgen insensitivity syndrome. Lancet. 2012; 380:1419-1428. - PubMed
    1. Boehmer AL, Brinkmann O, Brüggenwirth H, van Assendelft C, Otten BJ, Verleun-Mooijman MC, Niermeijer MF, Brunner HG, Rouwé CW, Waelkens JJ, Oostdijk W, Kleijer WJ, van der Kwast TH, de Vroede MA, Drop SL. Genotype versus phenotype in families with androgen insensitivity syndrome. J Clin Endocrinol Metab. 2001; 86:4151-4160. - PubMed
    1. Singh S, Ilyayeva S. Androgen Insensitivity Syndrome. In: StatPearls,Treasure Island (FL). 2023.
    1. Hornig NC, Ukat M, Schweikert HU, et al. . Identification of an AR mutation-negative class of androgen insensitivity by determining endogenous AR activity. J Clin Endocrinol Metab. 2016; 101:4468-4477. - PMC - PubMed