ESPE Abstracts (2019) 92 P1-412

WES Analysis of a Cohort of 94 Patients Presenting with 46,XY and 46,XX DSD

Patrick Sproll1, Brian Stevenson2, Serge Nef3, Anna Biason-Lauber1


1Division of Endocrinology, Department of Medicine, University of Fribourg, Fribourg, Switzerland. 2Swiss Institute of Bioinformatics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. 3Department of Genetic Medicine & Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland


Background: Disorders/Differences of Sex Development (DSD) is diagnosed in approximately one out of 4'500 newborns. Children born with DSD present with a very diverse phenotype and they and their families face considerable challenges, potentially including surgical intervention and gender assignment, as well as associated complications such as infertility and predisposition to gonadal tumors. Due to the lack of knowledge concerning the complete gene and protein pathways involved in sex development and DSD, causative genetic variants currently can only be identified in about 50% of the affected patients.

Methods: Whole exome sequencing (WES) was performed on a large cohort of 96 46,XY and 46,XX DSD patients in order to identify new genes and variants implicated in DSD. By applying different filtering methods, variants in known DSD genes as well as variants in new genes potentially causative for DSD, were identified.

Results: For 26 patients, causative genetic variants in previously known DSD genes could be identified. Additionally, 40 new potential candidate genes for DSD were identified based on the number of patients carrying variants, the similarity of the phenotype, the pathogenicity prediction and their expression in tissues important for sex development (e.g. gonads and pituitary), like CCDC88C.

Conclusion: WES is an important tool that allows for the identification of new genes potentially involved in DSD, advancing our understanding of human sex development and our capacity to accurately diagnose, support and treat patients and their families.

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