hrp0092s3.3 | Novel Insights in Our Understanding of Disorders of Sex Development: From Genes to Clinical Outcomes | ESPE2019

Novel Insights into Sex Determination: Mutual Antagonism of Pro-Testis and Pro-Ovary Signalling Pathways

Greenfield Andy

There is no single conception of sex that covers the multitude of biological process that are commonly encompassed by the term and its cognates. Gonadal sex determination is sometimes known as 'primary' sex determination due to its centrality in our understanding of 'maleness' and 'femaleness'. In mammals, this is characterised by the sexually dimorphic development of an initially bipotential gonadal primordium in the fetus into either a testis or an ov...

hrp0094p1-49 | Sex Endocrinology and Gonads A | ESPE2021

Biallelic PPP2R3C mutations are associated with partial and complete gonadal dysgenesis in 46,XY and 46,XX individuals

Cicek Dilek , Warr Nick , Yesil Gozde , Eker Hatice Kocak , Bas Firdevs , Poyrazoglu Sukran , Darendeliler Feyza , Direk Gul , Hatipoglu Nihal , Eltan Mehmet , Tosun Busra Gurpinar , Kaygusuz Sare Betul , Menevse Tuba Seven , Turan Serap , Bereket Abdullah , Greenfield Andy , Guran Tulay ,

Context: PPP2R3C encodes the B”gamma regulatory subunit of the protein phosphatase 2A (PP2A), which is a serine/threonine phosphatase involved in the phospho-regulation processes of mammalian cells. We have recently reported homozygous and heterozygous mutations in PPP2R3C in patients with syndromic 46,XY complete gonadal dysgenesis (MEGD syndrome) and impaired spermatogenesis, respectively. In this study, we have further investigated th...

hrp0092fc10.3 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

Mutations in the DEAH-box RNA Helicase DHX37 are a Frequent Cause of 46,XY Gonadal Dysgenesis and 46,XY Testicular Regression Syndrome

McElreavey Ken , Jorgensen Anne , Eozenou Caroline , Merel Tiphanie , Bignon-Topalovic Joelle , Tan Daisy , Houzelstein Denis , Buonocore Federica , Warr Nigel , Kay Raissa , Peycelon Mathieu , Siffroi Jean-Pierre , Mazen Inas , Achermann John , Shcherbak Yuliya , Leger Julienne , Sallai Agnes , Carel Jean-Claude , Martinerie Laetitia , Le Ru Romain , Conway Gerald , Mignot Brigitte , Van Maldergem Lionel , Bertalan Rita , Globa Evgenia , Brauner Raja , Jauch Ralf , Nef Serge , Greenfield Andy , Bashamboo Anu

XY individuals with Disorders/Differences of Sex development (DSD) are characterized by reduced androgenization caused, in some children, by gonadal dysgenesis or, more rarely, testis regression during early fetal development. The genetic etiology for most patients with 46,XY gonadal dysgenesis and for all patients with testicular regression syndrome (TRS) is unknown. Identification of novel genes involved in DSD is crucial for providing an accurate clinical diagnosis, aiding ...

hrp0089p1-p216 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology P1 | ESPE2018

SDgeneMatch, A New Tool to Aid the Identification of the Genetic Causes of DSD

De Ridder Jeroen , Bashamboo Anu , Baere Elfride De , Krone Nils , Mitchell Rod , Meyts Ewa Rajpert-De , Tobias Ed , Looijenga Leendert , Achermann John , Werner Ralf , Ahmed Faisal , Hiort Olaf , Greenfiled Andy , McElreavey Ken

Currently, the majority of patients with DSD do not have a molecular diagnosis. Although high throughput sequencing is having an impact on the clinical diagnosis of DSD the accurate interpretation genomic datasets of the identification of new gene mutations causing DSD is challenging. This is due to emerging evidence that DSD may be caused by mutations in many different genes and the prevalence of mutations in a single gene may be very low. As larger number of DSD patients are...