ESPE Abstracts

Background: Central diabetes insipidus (CDI) in the neonatal age is usually a result of intracranial insult, either congenital or acquired. Familial CDI is usually an autosomal dominant disorder, presenting later in childhood (1-6 y) with polyuria and mostly caused by mutations in the Neurophysin II moiety of the AVP-NPII prohormone gene; these interfere with prohormone processing leading to gradual destruction of AVP secreting cells and result in arginine vas...

Introduction: Patients homozygous for mutation in the PCSK-1 gene present clinically with severe congenital diarrhea and variable hormonal defects due to lack of enzyme/prohormone processing by Prohormone Convertase 1/3 (PC1/3). Although absence of spontaneous puberty has been reported in patients with PCSK-1 mutations, no peptide hormone(s) in the hypothalamus-pituitary-gonadal axis (HPG) have been reported to be dependent on PC1/3 cleavage. Here we studied t...

Background: Though the genes and signalling pathways involved in sexual development have only been partially elucidated, it is known that their disruption can result in disorders of sexual development (DSD). XX ovarian dysgenesis (XX-OD) is a rare, genetically heterogeneous disorder characterized by underdeveloped and dysfunctional ovaries. We previously identified a novel missense mutation in Nucleoporin107 (Nup107, c.1339G>A, p.D447N), an essential compo...

Background: NKX2-2 gene mutation (reported in 3 cases worldwide) cause severe IUGR and neonatal diabetes. Beta-cells of the mice Nkx2-2 (−/−) model were recently shown to convert into cells producing the appetite-promoting peptide ghrelin. Classically, ghrelin secretion is stimulated during fast and suppressed by nutrients or glucose ingestion in all age groups. In obese children this ghrelin suppression reaches a minimum of 60% of base...

Background: 5-alpha-reductase-2 (5α-RD2) deficiency is an autosomal recessive 46,XY disorder of sexual development, characterized by undervirilized prepubertal males with ambiguous genitalia. The pubertal rise in testosterone and 5α-RD1 isoenzyme activity causes virilization, often resulting in gender assignment change. Early precise diagnosis which anticipate adult function is critical for treatment and gender assignment.Objective and hypothes...

Background: SGA is defined as birth weight under 2 standard deviations (SD) from the mean. Previous studies indicate that 10% of SGA babies do not have “catch-up growth” (CUG). They are eligible for growth hormone (GH) therapy to increase final height. The unexpected low demand for GH therapy in SGA babies, triggered us to survey the actual incidence of SGA and failure in CUG.Objective and hypotheses: To find the actual incidence of SGA and fai...

Background: Wolfram syndrome type 2 (WFS2) characterized by childhood GI ulcers/ bleeding, diabetes, and neurodegeneration with optic atrophy and hearing loss was recently elucidated as caused by CISD2/NAF-1 gene mutation. NAF-1 suppression in cells results in intra-mitochondrial accumulation of iron, increased ROS generation and consequently increased cellular apoptosis. So far only two mutations in four families were reported.Objective: Elucidate the c...

Background: Mutations in the gene HSD17B3 encoding the 17-beta hydroxysteroid dehydrogenase 3 enzyme cause testosterone insufficiency leading to XY DSD. In this study the clinical characteristics and molecular etiology of 3 new severe XY DSD cases from consanguineous families are elucidated.Clinical report: Three female patients (2 sisters and a single unrelated female) presented at ages 0.1, 8 and 0.7 years with ambiguo...

Accumulating evidence supports a causal role for the human gut microbiome in obesity, diabetes, metabolic disorders, cardiovascular disease, and numerous other conditions. I will present our research on the role of the human microbiome in health and disease, ultimately aimed at developing personalized medicine approaches that combine human genetics, microbiome, and nutrition. In one project, we tackled the subject of personalization of human nutrition, using a cohort of over 1...

Background: Congenital hypothyroidism is a common condition with reported incidence between 1/2000 – 1/4000 live births. In approximately 85% of cases this is sporadic due to a structural abnormality of the thyroid gland. Approximately 15% of cases are hereditary and secondary to thyroid dyshormonogenesis. Most of these are due to mutations in one of the genes involved in iodine transport or organification, mutations in the thyroglobulin gene or d...