ESPE Abstracts

Background: The process of sexual differentiation is critical for reproduction in nearly all metazoan. Defects in any of the genes involved in either testicular or ovarian development can result in disorders of sex development (DSD). CBX2/M33 is a chromatin modifier that plays an important role in sexual development and its disorders, highlighted by the fact that M33-deficient mice have male-to-female sex reversal and loss-of-function of CBX2 causes 46, XY DSD...

Background: The process of sexual differentiation is critical for reproduction in nearly all metazoan. Defects in any of the genes involved in either testicular or ovarian development can result in disorders of sex development (DSD). CBX2/M33 is a chromatin modifier that plays an important role in sexual development and its disorders, highlighted by the fact that M33-deficient mice have male-to-female sex reversal and loss-of-function of CBX2 causes 46, XY DSD in humans. Human...

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...

Background: Differentiation of the gonads in men is closely dependent on Sertoli cells maturation. Differences of sex development (DSD) are caused by variations in this process. 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. However, there are two main obstacles for the study of human Sertoli cells. Firstly, mature human Sertoli cells lose their proliferation...

Background: Steroidogenic factor 1 (SF-1/NR5A1) plays a crucial role in regulating adrenal development, gonad determination and differentiation, and in the hypothalamic-pituitary control of reproduction and metabolism. In men (46, XY) mutations in SF-1/NR5A1 gene cause a wide phenotypic spectrum that ranges from complete testicular dysgenesis with Müllerian structures and amenorrhea, through individuals with mild clitoromegaly or genital ambiguity, to severe penoscrotal h...

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...

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...

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 ...

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...

Background: An activation cascade of specific genes sets up the initiation of sex determination leading in males to testes formation and synthesis of testicular hormones. Disruption of this gene cascade may cause a spectrum of 46,XY disorders/differences of sex development (DSD) phenotypes. Here we describe for the first time two sisters suffering from 46,XY DSD, who by whole exome sequencing revealed to carry a X-linked mutation in the StAR-related lipid transfer domain prote...