ESPE Abstracts

Background: Homozygous mutations in STAT5B result in GH insensitivity and immune dysfunction. Heterozygous dominant negative mutations have not been described.Aims and objectives: To characterize genomic STAT5B DNA in two families exhibiting short stature.Methods: Sanger sequencing of STAT5B from genomic DNA. Mutant STAT5B constructs were expressed in HEK293 cells.Results: ...

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: Heterozygous mutations in the IGF1 receptor (IGF1R) are often associated with congenital IGF1 resistance, causing variable degrees of intrauterine growth retardation (IUGR) and postnatal short stature. To date, only one homozygous IGF1R mutation has been reported, in a child presenting with severe growth failure, mild intellectual impairment, microcephaly, dysmorphic features, and cardiac malformations.Objective: We now repo...

Background: Primary IGF1 deficiency can result from molecular defects in genes encoding for the GHR, IGF1, STAT5b and ALS. Heterozygous, activating mutations in the STAT3 gene have been recently described in children with severe growth failure associated with a spectrum of early-onset autoimmune disease.Case presentation: We report the molecular diagnosis in two unrelated patients with severe growth failure and IGF1 deficiency: P1, a 3.6 year ol...

Context: Severe forms of growth hormone insensitivity (GHI) are characterised by extreme short stature, dysmorphism and metabolic anomalies. They are classically caused by homozygous or compound heterozygous mutations of the growth hormone receptor gene (GHR). Genetic analysis traditionally focuses on the exonic regions of genes that encode proteins rather than the intervening non-coding sequences. These seldom explored non-coding regions may harbour ...

Background: We have recently reported the molecular diagnosis of two patients with severe growth failure associated with a spectrum of early-onset autoimmune disease and immunodeficiency. Heterozygous de novo mutations, c.1847_1849delAAG (p.E616del) and c.1276T>C (p.C426R), in the STAT3 gene were found. Functional in vitro studies of these variants are presented.Objective and hypotheses: We...

Background: PAPP-A2 is a metalloproteinase that specifically cleaves IGFBPs 3 and 5. Papp-a2 knock-out (KO) mice show a reduction in body size and skeletal abnormalities.Objective and hypotheses: Our objective is to report two affected families from Spain and USA. The Spanish family presents a homozygous frameshift mutation in exon 3 of the PAPP-A2 gene (c.1927_ 1928insAT, p.D643fs25X) resulting in a premature stop codon, with 2 of 4 si...

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...

Rapid-onset obesity with central hypoventilation, hypothalamic, autonomic dysregulation (ROHHAD) syndrome is a rare disorder characterized by respiratory failure and autonomic dysregulation with endocrine abnormalities. Some of these patients could also present with neuroendocrine tumors (ROHHADNET).Aim: To evaluate the clinical, biochemical, treatments and outcome in a cohort of pediatrics patients with ROHHAD-NET syndrome follow in a s...

Purpose: The 3-month gonadotropin-releasing hormone analogs (GnRHa) are expected to achieve better compliance in central precocious puberty (CPP) patients, but the 1-month depot remains the dominant choice for conventional treatment worldwide. Our study aimed to investigate the long-term efficacy of 3-month GnRHa for the treatment of CPP.Methods: In this retrospective study, 69 Korean girls diagnosed with CPP were includ...