title: Review disorders of sex development: The evolving role of genomics in diagnosis and gene discovery.
abstract: Disorders of Sex Development (DSDs) are a major paediatric concern and are estimated to occur in around 1.7% of all live births (Fausto-Sterling, Sexing the Body: Gender Politics and the Construction of Sexuality, Basic Books, New York, 2000). They are often caused by the breakdown in the complex genetic mechanisms that underlie gonadal development and differentiation. Having a genetic diagnosis can be important for patients with a DSD: it can increase acceptance of a disorder often surrounded by stigma, alter clinical management and it can assist in reproductive planning. While Massively Parallel Sequencing (MPS) is advancing the genetic diagnosis of rare Mendelian disorders, it is not yet clear which MPS assay is best suited for the clinical diagnosis of DSD patients and to what extent other established methods are still relevant. To complicate matters, DSDs represent a wide spectrum of disorders caused by an array of different genetic changes, many of which are yet unknown. Here we discuss the different genetic lesions that are known to contribute to different DSDs, and review the utility of a range of MPS approaches for diagnosing DSD patients. Birth Defects Research (Part C) 108:337-350, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Murdoch Children's Research Institute, Melbourne, Victoria, Australia and The Hudson Institute of Medical Research, Monash University, Melbourne, Victoria, Australia.
authors.forename: Brittany
authors.initials: B
authors.lastname: Croft
authors.affiliation: Murdoch Children's Research Institute, Melbourne, Victoria, Australia and Department of Paediatrics, University of Melbourne, Victoria, Australia.
authors.forename: Katie
authors.initials: K
authors.lastname: Ayers
authors.affiliation: Murdoch Children's Research Institute, Melbourne, Victoria, Australia and Department of Paediatrics, University of Melbourne, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sinclair
authors.affiliation: Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ohnesorg
mesh_terms: D000818:Animals; D056915:DNA Copy Number Variations; D012734:Disorders of Sex Development / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D023281:Genomics / Q000379:methods; D006058:Gonadal Disorders / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D046468:Sexual Development / Q000235:genetics
keywords: Disorders of Sex Development; genetic diagnosis; gonadal dysgenesis; massive parallel sequencing; ovary; testis