ESPE Abstracts

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...

Introduction: Rare mutations of the ESR1gene, encoding the estrogen receptor alpha (ERα), have been shown to cause estrogen resistance in humans. To date, there are no effective therapeutic options. We report the case of a new inactivating mutation of ERα and provide evidence for a partial restoration of biological effects of estrogen.Methods: We performed clinical and biological phenotyping of the index case and sequenced the ESR1...

Background: Hypospadias is a common characteristic of Disorders of Sex Development (DSD). At the present time a molecular diagnosis is not reached in over 50% of cases. The DDD Study represents a useful resource of large molecular and phenotypic datasets obtained from individuals with an undiagnosed developmental abnormality including DSD.Objective: To review associated features and identify likely pathogenic variants in previously undiagnosed DDD partic...

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...

Background: 46,XY gonadal dysgenesis (GD) is a spectrum disorder which lead to variable degrees of atypical external genitalia, ranging from female to micropenis and absent of gonadal tissue (known as Embryonic Testicular Regression Syndrome -ETRS). Most patients with 46,XY GD remains without a molecular diagnosis.Objective: To report the DEAH-box helicase 37 gene (DHX37) as a novel candidate for the GD etiology.Patients a...

Increasing evidence suggests that the aetiology of disorders of sex development cannot be solely explained by genetic alterations. It is highly likely that environmental factors hitting susceptible genetic backgrounds are partly causative. Zebrafish sex is highly plastic during development, making this species an ideal model for investigation of endocrine disruption and gonadal development and function. However, the hormonal regulation of these processes in zebrafish is poorly...