ESPE Abstracts

Background: ALS deficient (ALS-D) patients present severe IGFI and IGFBP3 deficiencies and variable degree of growth retardation. Heterozygous carriers for IGFALS variants, ALS-D relatives or a subset of ISS children, have levels of IGFI, IGFBP3 and ALS intermediate between ALS-D and wildtype (WT) subjects. This supports that IGFALS gene variants may affect ALS synthesis, secretion and/or function and could be responsible for the observed phenotype.<p cla...

Diabetes mellitus is a pandemic metabolic disorder characterized by chronic hyperglycemia. The pathogenic process is the result of insulin insufficiency. Insulin is a peptide hormone produced in the beta cells of the pancreatic islets. Current diabetes treatments strive for glycemic control but fail to solve the underlying beta cell defect. This approach has increased the life expectancy and quality of most patients with diabetes but has turned diabetes into a chronic disease....

Introduction: Variants in the N-terminal of the Indian-hedgehog gene (IHH) have been associated with Brachydactyly type-A1 (AD) and Acrocapitofemoral dysplasia (AR), only three of which have been functionally studied. However, heterozygous IHH variants, majority classified as variants of unknown significance (VUS) are being increasingly identified, not only in the N-terminal but also in the uncharacterized C-terminal, by NGS, in individuals with short...

Background: Follicle-stimulating hormone (FSH) plays a key role in reproduction. The G-protein coupled FSH receptor (FSHR), is expressed primarily in gonads, and specifically binds FSH. FSHR is also expressed in vascular endothelium, osteoclasts, adipose tissue, monocytes and rodent pancreatic islets. Elevated FSH levels are associated with development of obesity, insulin resistance, osteoporosis, and cardiovascular disease. In a recent study, we showed that h...

Type 1 diabetes mellitus is autoimmune T cells mediated destruction of β-cells. Mesenchymal stem cells (MSCs) are considered a promising treatment for T1DM due to the strong immunosuppressive and regenerative capacity. However, the comprehensive mechanism is still unclear. Our previous study indicated that the transforming growth factor beta-induced gene (TGFBI) is highly expressed in human umbilical cord derived mesenchymal stem cells (hUC-MSCs), which is also implicated...

Introduction: The thyrotropin receptor (TSHR) has a key role in the thyroid gland. It is involved in folliculogenesis, differentiation, organogenesis, and thyroid hormone synthesis and production. Its genetic defects can cause poor differentiation (thyroid dysgenesis) and/or thyroid malfunction (thyroid dyshormonogenesis, TD). Therefore, its phenotype spectrum is wide, ranging from severe congenital hypothyroidism (CH) to mild hyperthyrotropinemia. Some hetero...

Human sex development relies on differentiation of the gonads, in which Sertoli and granulosa cells play a key role for men and women respectively. Many variations of sex development (VSD) are due to alteration of these two cell types. The study of the mechanisms underlying these conditions is crucial for optimal clinical management of VSDs, as for more than 50% [1] of all VSD patients, the molecular cause of their condition remains unknown. The collection of primary cells is ...

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...

Introduction: Obesity increases the risk of various disorders including diabetes, non-alcoholic fatty liver disease (NAFLD) and cardiovascular disorders. MicroRNAs (miRNA) are single-stranded, non-coding oligonucleotides that regulate gene expression. Sirtuin 1 (SIRT1), a regulatory enzyme in metabolic homeostasis, is regulated by miRNAs. The aim of this study was to evaluate miR-141 in obesity and whether this miRNA can regulate SIRT1 expression.Materia...

Background: Aromatase (CYP19A1) a member of cytochrome P450 protein family is a major steroid metabolizing enzyme which converts androgens to estrogens. Mutations in aromatase can lead to autosomal recessive aromatase deficiency. An R192H mutation in CYP19A1 described earlier caused severe phenotype of aromatase deficiency with regressive virilization of the 46,XX new-born, but without signs of androgen excess during pregnancy. Computational studies suggested that R192H disrup...