Update on the genetics of differences of sex development (DSD) Dorien Baetens a, b , Hannah Verdin a , Elfride De Baere a , Martine Cools b, * a Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium b Division of Pediatric Endocrinology, Department of Internal Medicine and Pediatrics, Ghent University Hospital and Ghent University, Ghent, Belgium article info Article history: Available online 13 April 2019 Keywords: differences of sex development gonadal dysgenesis developmental genetics steroidogenesis massively parallel sequencing Human gonadal development is regulated by the temporospatial expression of many different genes with critical dosage effects. Subsequent sex steroid hormone production requires several consecutive enzymatic steps and functional hormone receptors. Disruption of this complex process can result in atypical sex development and lead to conditions referred to as differences (disorders) of sex development (DSD). With the advent of massively parallel sequencing technologies, in silico protein modeling and innovative tools for the generation of animal models, new genes and pathways have been implicated in the pathogenesis of these conditions. Here, we provide an overview of the currently known DSD genes and mechanisms involved in the process of gonadal and phenotypical sex development and high- light phenotypic findings that may trigger further diagnostic investigations. © 2019 Elsevier Ltd. All rights reserved. Introduction Human gonadal development is a highly complex and intriguing process: depending on the pres- ence or absence of a Y chromosome, and more specifically of the Sex Determining gene on Y (SRY) gene * Corresponding author. E-mail address: martine.cools@ugent.be (M. Cools). Contents lists available at ScienceDirect Best Practice & Research Clinical Endocrinology & Metabolism journal homepage: www.elsevier.com/locate/beem https://doi.org/10.1016/j.beem.2019.04.005 1521-690X/© 2019 Elsevier Ltd. All rights reserved. Best Practice & Research Clinical Endocrinology & Metabolism 33 (2019) 101271