hrp0092p1-412 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology (2) | ESPE2019

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

Sproll Patrick , Stevenson Brian , Nef Serge , Biason-Lauber Anna

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 pr...

hrp0084fc6.4 | Gonads & DSD | ESPE2015

Severe 46,XY Disorder of Sex Development due to CBX2 Isoform 2 Mutation is Distinct from CBX2.1 Deficiency and is Likely due to EMX2 Dysregulation in the Human Developing Gonad

Eid Wassim , Costa Elaine , Sproll Patrick , Lauber-Biason Anna

Background: The process of sexual differentiation is central for reproduction of almost all metazoan. Recently, we identified CBX2.1 a chromatin architecture regulator, as an essential transactivator for human male gonadal development. CBX2 has a second isoform CBX2.2. Since nothing is known about the role of CBX2.2 in human sex development, we took advantage of the p.C132R mutation in CBX2.2 in a 46,XY disorder of sex development (DSD) patient with complete female phenotype a...

hrp0092fc10.5 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

Transcriptome Analysis of Novel Sertoli Cell Models to Highlight Potential Genes Involved in DSD Mechanism of Disease

Gutiérrez Daniel Rodríguez , Sproll Patrick , Biason-Lauber Anna

Background: Determination of the gonads in men is closely dependent on Sertoli cells differentiation and maturation. Many cases of differences of sex development (DSD) are caused by variations in these processes. The study of the mechanisms underlying these complex conditions is crucial for optimal clinical management and Sertoli cells would be an ideal model for this purpose. Our human Sertoli-like cell model (SLCs) may shed some light on the identification o...

hrp0092rfc10.5 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

VVariants in NWD1 Gene Leading to Different Degrees of Gonadal Dysgenesis

Aeppli Tim , Gaisl Odile , Sproll Patrick , Lang-Muritano Mariarosaria , Nef Serge , Konrad Daniel , Biason-Lauber Anna

Introduction: Mammalian sex development is directly dependent on gonadal determination. Whole exome sequencing in patients with differences of sex development (DSD) allows the discovery of new factors involved in human sex development. One of these factors is NWD1 (NACHT and WD repeat domain containing 1) a cytosolic protein that seems to play a role in modulating androgen receptor signaling. We identified variants in the NWD1 gene in six und...

hrp0092p2-271 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

Follow-Up of Two Similar Patients with Steroidogenic Factor-1 (SF-1/ NR5A1) Variants, in Two Different Eras

Gaisl Odile , Aeppli Tim , Sproll Patrick , Lang-Muritano Mariarosaria , Nef Serge , Konrad Daniel , Biason-Lauber Anna

Abstract: Steroidogenic factor 1 (SF1)/"nuclear receptor subfamily 5 group A member 1" (NR5A1) is involved in adrenal and gonadal development, steroidogenesis and reproduction. The first patient, published in 1999 presented with a 46,XY difference of sex development (DSD) and adrenal insufficiency. The following year the first female patient with only adrenal insufficiency was described. Since then, heterozygous changes in SF-1/NR5A1 causing 46,XY DSD ...

hrp0089fc8.1 | Sex differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2018

Estrogen Receptor 2 Variant as a Novel Cause for Dysgenetic Ovaries

Lang-Muritano Mariarosaria , Sproll Patrick , Wyss Sascha , Kolly Anne , Hurlimann Renate , Konrad Daniel , Biason-Lauber Anna

Background: Variants in the estrogen receptor α (ESR1) have previously been described in male and female patients presenting with estrogen resistance. Estrogen resistance is characterized by delayed bone-age, early-onset osteoporosis, delayed puberty and multicystic ovaries in women. So far, no clinical consequences of variants in the estrogen receptor β (ESR2) have been reported in 46,XX patients, although ESR2 variants have previously been implicated in 46,XY DSD p...

hrp0084p1-60 | DSD | ESPE2015

Insight into the Human Ovarian Sex Development Networks

Bouazzi Leila , Franco Mariangela , Eid Wassim , Meyer-Boni Monika , Sproll Patrick , Maret Alexander , Lauber-Biason Anna

Background: Ovarian sex differentiation network involves a panoply of interacting factors. Yet, no single sex-determining factor has been identified to be an equivalent of SRY or SOX9 in the testis. Recently, data suggested CBX2 as a pioneer regulator promoting testis development. In addition to its implication in ovary pathway differentiation which remains unclear.Objective and hypotheses: To deepen our understanding of the regulatory network that under...

hrp0094p2-396 | Sex differentiation, gonads and gynaecology or sex endocrinology | ESPE2021

Combining big data science with clinics: Novel approach for understanding human sex development and its variants.

Rodriguez Gutierrez Daniel , Sproll Patrick , Von der Decken Isabel , Stevenson Brian , Lang-Muritano Mariarosaria , Konrad Daniel , L’Allemand Dagmar , Nef Serge , Biason-Lauber Anna ,

Background/Introduction: Whole exome sequencing (WES) revolutionized clinical genetics in patients with differences of sex development (DSD). However, our ability to interpret WES data is limited by our incomplete understanding of the mechanisms involved in DSD. Thus, we created a methodology that scores potential candidates based on single cells transcriptomics of human male gonadal cells and applied it to WES data from a cohort of genetically male (46,XY) DS...