https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)60071-3.pdf

Androgen insensitivity syndrome

Interaction Modules Directing Cell Regulation Kim Van Roey,† Bora Uyar,† Robert J. Weatheritt,‡ Holger Dinkel,† Markus Seiler,† Aidan Budd,† Toby J. Gibson,† and Norman E. Davey*,†,§ †Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany ‡MRC Laboratory of Molecular Biology (LMB), Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom Department of Physiology, University of California, San Francisco, San Francisco, California 94143, United States

Short linear motifs: ubiquitous and functionally diverse protein interaction modules directing cell regulation.

Androgen insensitivity syndrome.

Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical Many of the genes required for gonad development have been identified by analysis of DSD patients However, the use of knockout and transgenic mouse strains have contributed enormously to the study of gonad gene function and interactions within the development network Although the genetic basis of mammalian sex determination and differentiation has advanced considerably in recent years, a majority of 46,XY gonadal dysgenesis patients still cannot be provided with an accurate diagnosis Some of these unexplained DSD cases may be due to mutations in novel DSD genes or genomic rearrangements affecting regulatory regions that lead to atypical gene expression Here, we review our current knowledge of mammalian sex determination drawing on insights from human DSD patients and mouse models

/pdf/mammalian-sex-determination-insights-from-humans-and-mice-835laqpoto.pdf

Mammalian sex determination—insights from humans and mice

Disorders of sex development

Background: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). Objective: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. Setting: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. Methods: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. Results: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%)...

/pdf/novel-60-and-recurrent-40-androgen-receptor-gene-mutations-4ljidx6dld.pdf

J. A. Bermúdez de la Vega

Papers

Novel (60%) and Recurrent (40%) Androgen Receptor Gene Mutations in a Series of 59 Patients with a 46,XY Disorder of Sex Development