Endocrine Abstracts

Background: SOX2 is a member of the SOX (SRY-related HMG box) family of transcription factors, and shares homology with SOX1 and SOX3 which are members of the SOXB1 subfamily. Heterozygous, de novo, loss-of-function mutations in SOX2 were initially reported in patients with bilateral anophthalmia/microphthalmia, developmental delay and male genital tract abnormalities, with variable manifestations including defects of the corpus callosum, oes...

Introduction: Hypoparathyroidism-retardation-dysmorphism syndrome (HRD) is an autosomal recessive disorder characterized by distinct clinical, biochemical, and genetic abnormalities. HRD has almost exclusively been reported in children of Middle Eastern origin where the rate of consanguinity is high. The syndrome is characterized by severe short stature, the aetiology of which is unclear. Mutations in tubulin-specific chaperone E (TBCE), a gene encoding a chaperone requ...

Mutations in GHR, STAT5B and IGF1 lead to GH-insensitivity but often the cause of reduced GH-sensitivity remains unknown. We describe the identification of a mutation in the MVK gene encoding mevalonate kinase (MK) in a pedigree investigated for STAT5B-deficiency.A 15-year-old male born to consanguineous parents was referred for short stature (height 125.8 cm; −5.6 SDS) and arthritis. He presented, aged 2 years, with fev...

Background: SOX3, a member of the SOXB1 subfamily of transcription factors, is a single-exon gene located on the X-chromosome and expressed in neuroepithelial and progenitor cells from the earliest stages. In mice, its expression in the infundibulum is important for the correct induction of Rathke’s pouch morphogenesis, with loss of function resulting in defects of CNS midline structures, teeth misalignment and variable hypopituitarism. We have previously demonstra...

Background and aim: The development of the pituitary gland is closely linked to this of the eyes and forebrain, as they all originate from the same embryonic origin, the anterior neural ridge. The constellation of symptoms leading to septo-optic dysplasia (SOD) is well established; other ophthalmic signs may be under-reported. The aim of the study was to define if patients with hypopituitarism present with eye abnormalities, which are distinct from SOD, and if this association...

Introduction: Anophthalmia/microphthalmia is a rare developmental craniofacial defect often associated to congenital hypopituitarism with GH deficiency and hypogonadism. SOX2 gene plays a key role in embryonic development regulation and heterozygous mutations of this gene, reported only in 14 patients to date, have been associated to anophthalmia/microphthalmia and congenital hypopituitarism in uo to 10% of cases. Therefore, the study of the SOX2 gene can be clinically useful ...

Introduction: Mutations affecting hypothalamic development in humans have been identified in genes that affect isolated domains of hypothalamic function leading to restricted phenotypes, such as obesity or hypogonadotrophic hypogonadism. We describe the first human cases of diabetes insipidus and combined pituitary hormone deficiency due to a mutation in a gene regulating hypothalamic development.Results: Six affected individuals from a highly consanguin...

Background: SOX2 is an early developmental transcription factor implicated in pituitary development. It consists of a N-terminal domain, a high mobility group (HMG)-DNA binding domain and a carboxyl-terminal domain. Heterozygous SOX2 mutations have been described in patients with a severe ocular phenotype and hypogonadotrophic hypogonadism (HH) with/without associated abnormalities. In vitro SOX2 interacts with β-catenin, a member of the Wnt signalling pathway, and...

Background and Aim: The development of the pituitary gland is closely linked to this of the eyes and forebrain, as they all originate from the same embryonic origin, the anterior neural ridge. The constellation of symptoms leading to septo-optic dysplasia (SOD) is well established; other ophthalmic signs may be under-reported. The aim of the study was to define if patients with hypopituitarism present with eye abnormalities, which are distinct from optic nerve hypoplasia (ONH)...

The nuclear receptor steroidogenic factor 1 (SF1/AdBP4/FTZF1, NR5A1) is a key regulator of adrenal and gonadal development, steroidogenesis and reproduction, and targeted deletion of Nr5a1 (Sf1) in the mouse results in adrenal and gonadal agenesis, XY sex-reversal and persistent Müllerian structures in males. Consistent with this phenotype, DNA-binding mutations in SF1 have been reported in two 46,XY female patients with primary adrenal failure and uterine s...