ESPE Abstracts

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...

Introduction: To investigate the protective effects of combined intervention with adenovirus vector mediated interleukin 10 (IL10) and IGF1 genes on islet β cells in nonobese diabetes (NOD) mice with type 1 diabetes mellitus (T1D) at early stage.Methods: Twenty-four female NOD mice at onset of diabetes and aged 17–20 weeks old were randomly divided into four groups. Mouse 1, 2, and 3 groups were i.p. injected 0.1 ml of Ad-mIGF1, Ad-mIL10, and c...

Introduction: To investigate the protective effects of combined intervention with adenovirus vector mediated interleukin 10 (IL-10) and insulin-like growth factor 1 (IGF1) genes on islet β cells in nonobese diabetes (NOD) mice with type 1 diabetes mellitus (T1D) at early stage.Methods: Twenty-four female NOD mice at onset of diabetes and aged 17–20 weeks old were randomly divided into four groups. Mouse 1, 2 and 3 groups were intraperitoneally ...

Background: Despite current treatment, girls and women with severe forms of 21OHD are exposed lifelong to a chronic excess of androgens and the secondary effects of suppressive corticoids, which make gene therapy (GT) an option to be explored.Objective: To evaluate the effect of human CYP21 gene transfer mediated by adeno-associated virus (AAV) in a Cyp21−/− mouse model.Methods: 17 adult <em...

Background: The adrenal cortex undergoes constant cellular renewal and any effect from recombinant adeno-associated vectors (rAAV) targeting differentiated cells will be transient as extra-chromosomal DNA will be lost by dividing cells. A novel option is to use rAAV to express ectopic adrenocortical enzymes in a stable organ outside the adrenal gland. Our aim was to correct the biochemical phenotype in a mouse model for congenital adrenal hyperplasia (CAH) wit...

The use of recombinant adeno-associated viruses (rAAV) as safe vectors have allowed hundreds of gene therapy attempts to treat monogenic diseases not including bone genetic diseases (Gao G, Nat Rev Drug Dis 2019). To our knowledge, there has been few attempts to apply gene therapy to monogenic bone diseases, largely because most skeletal malformations are being developed during fetal life. Patients affected with acrodysostosis are known to aggravate their skeletal malformation...

Objective: To investigate the clinical and molecular characteristics of a girl with aldosterone synthase deficiency type II (ASDII). We also identified the consequences of a novel splice site mutation in the CYP11B2 gene.Materials and Methods: A4-month-old girl presented with vomiting, diarrhea, and failure to thrive. Her 17α-OHP, cortisol, renin, and aldosterone were all in the normal range, and the ACTH stimulatio...

Objective: X-linked agammaglobulinemia (XLA) is a kind of primary immunodeficiency disease caused by mutations in the gene encoding Bruton agammaglobulinemia tyrosine kinase (BTK). This study, we identified a novel in frame deletion mutation in exon11, c.902 _ c.904 delAAG(p.e301 _ g302 delinsG) in BTK gene and evaluated the function of BTK.Methods: A five-year-old boy presented with recurrent respiratory tract infections. His height wa...

Background: X-linked adrenoleukodystrophy (X-ALD) presents with two phenotypes: i) an adult form (adrenomyeloneuropathy, AMN), that involves axonal tracts without demyelination within the spinal cord and affects adult males and more than 80% of X-ALD heterozygote women in adulthood resulting in severe paraplegia. This far the most frequent form of X-ALD. Addison’s disease is very rare in X-ALD women but frequent in adult AMN males, very often with onset years or decades b...