ESPE Abstracts

Background: Insulin-like growth factor I (IGF-I) is one of the important hormonal mediators of human growth. Circulating IGF-I exists in a ternary complex bound to the acid-labile subunit (ALS) and one of its six binding proteins (BPs). IGF-I bound to ALS and BPs needs to be liberated by either Pregnancy Associated Plasma Protease A (PAPP-A) or A2 (PAPP-A2) to reach its receptor. Stanniocalcin 2 (STC2) is a potent inhibitor of both PAPP-A and PAPP-A2. Genome-wide association s...

Background: The type I IGF1R plays a role in intrauterine and postnatal growth. Heterozygous IGF1R mutations have been identified in over 20 families. Some of them are linked to the etiology of short stature in previous studies. In addition, we previously reported that a heterozygous nonsense mutation (p.Q1250X) of the IGF1R gene led to decrease IGF1R protein expression through endoplasmic reticulum-associated protein degradation (ERAD) mechanism, resulted in...

Background: The growth hormone-insulin-like growth factor (GH-IGF) axis plays a crucial role in bone growth, as evidenced by the phenotypes of patients with pathogenic IGF1 receptor (IGF1R) gene variants. These mutations lead to pre- and post-natal growth impairment and short stature. However, the molecular mechanisms of IGFs on human growth plate chondrocytes remain unclear, mainly due to the lack of tissue samples from healthy children.<p class=...

Background: Silver Russell syndrome (SRS) is genetically heterogenous and around 30% of patients with clinical SRS have no genetic diagnosis. Mutations in HMGA2 have recently been identified causing growth failure and an SRS-like phenotype. Despite strong evidence of the crucial role of HMGA2 in growth across species, the mechanism of action of HMGA2 in human linear growth is unclear.Objective:...

Background: Silver Russell syndrome (SRS) is a heterogeneous disorder characterised by intrauterine and post-natal growth retardation, relative macrocephaly, protruding forehead, feeding difficulties and body asymmetry. Variants in HMGA2 are a rare cause of SRS and despite strong evidence for the crucial role of HMGA2 in growth regulation, its functional role in human linear growth is unclear.Methods: Patients w...