Concordance of phenotypic expression and gender identity in a large kindred with a mutation in the androgen receptor

Hooper, Helen, Figueiredo, Bonald, Pavan-Senn, Carla, De Lacerda, Luiz, Sandrini, Romolo, Mengarelli, J. K., Japp, Anne and Karaviti, Lefkothea (2004) Concordance of phenotypic expression and gender identity in a large kindred with a mutation in the androgen receptor. Clinical Genetics, 65 (3). pp. 183-190. ISSN 0009-9163

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Abstract

A 14-year-old female presented to the Pediatric Endocrine Clinic, Universidade Federal o Parana Curitiba, Brazil, for obesity. A few years later, despite normal breast development, the patient had failed to menstruate and lacked pubic and axillary hair. Laboratory analyses revealed high levels of testosterone. Karyotype analysis was XY. Direct sequencing of her genomic DNA showed a G to T transition at nucleotide 2089 at exon 2 in the androgen receptor gene, resulting in a substitution of Phe for Cys at position 576. This mutation disrupts the first Zn finger critical to DNA binding and transcriptional activity and results in complete androgen-insensitivity syndrome (CAIS). This individual was part of 700-member multigenerational kindred of German origin living in small villages in Southern Brazil. Family members who gave informed consent were screened using a polymerase chain reaction-based method. Nineteen CAIS-affected individuals and carriers were identified. All presented with infertility and lack of or sparse pubic hair. The prevalence of common AIS within the kindred greatly exceeds that of the general population and is due in part to their isolated familial and community structures. All individuals are genuinely feminine in their appearance, sex behavior, gender identity, and integration within their communities. We conclude that CAIS leads to complete feminization of XY individuals and results in individuals who are psychologically and socially established and integrated as women within the familial and cultural contexts of their communities.

Item Type:	Article
Uncontrolled Keywords:	Androgen receptor; Androgen-insensitivity syndrome; Gender identity; Genotype-phenotype discordance; Polymerase chain reaction; Sex assignment
Subjects:	C400 Genetics
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Becky Skoyles
Date Deposited:	03 Feb 2015 16:48
Last Modified:	12 Oct 2019 17:30
URI:	http://nrl.northumbria.ac.uk/id/eprint/19664

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