ESPE Abstracts

We report the case of a 19 years old male patient suffering from a multisystem disease involving of the skeleton, connective tissue, immune system, brain and endocrine system due to compound-heterozygote mutations in the NBAS (Neuroblastoma amplified sequence) gene (c.5741G>A [p.(Arg1914His)]; c.6565_6566insT [p.(Glu2189Valfs*7)]), detected using whole-exome-sequencing. He has an immunodeficiency including decreased CD4+T-cells, B-cells and NK-cells with expanded ...

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: Cytochrome P450 side-chain cleavage enzyme (CYP11A1 gene) catalyses the conversion of cholesterol to pregnenolone in steroidogenic cells, the first step in the biosynthesis of all steroid hormones. SCC deficiency has been established as an autosomal recessive disorder caused by inactivating homozygous or compound heterozygous mutations in the CYP11A1 gene, with a wide phenotypic spectrum ranging from prematurity, complete underandrogenization and severe early-onset...

Background: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development and are associated with a variety of phenotypes, ranging from phenotypic women (complete androgen insensitivity syndrome) to milder degrees of undervirilization (partial and mild forms).Aims and objectives: To specify how a phenotype-genotype correlation can be refined by in vitro study based on the nature of amino acid substitutio...

Background: Age at menarche in girls varies widely between individuals, is a heritable trait and is associated with risks for adult obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality.Objective and Hypotheses: The mechanisms that determine pubertal timing and underlie its links to later disease remain unclear.Method: We performed a genome-wide association study meta-analysis of genome-wide or den...

Background: Ovarian sex differentiation network involves a panoply of interacting factors. Yet, no single sex-determining factor has been identified to be an equivalent of SRY or SOX9 in the testis. Recently, data suggested CBX2 as a pioneer regulator promoting testis development. In addition to its implication in ovary pathway differentiation which remains unclear.Objective and hypotheses: To deepen our understanding of the regulatory network that under...

Background: ‘Dead in Bed syndrome’ mechanism in childhood diabetes remains unknown. The hypothesis is that a nocturnal hypoglycaemia could lead to arrhythmias related to abnormal ventricular repolarisation.Objective and hypotheses: To look for a relationship between spontaneous fluctuations of nocturnal glycaemia, ventricular repolarization and heart rate variability (HRV) in prepubertal children with type 1 diabetes.Meth...

Background: Pubertal virilization in a 46,XY DSD patient is generally due to partial androgen insensitivity, 5-alpha-reductase deficiency, or 17-ketoreductase deficiency. Recently, reports have identified virilization signs associated with NR5A1/SF-1 gene mutations.Cases presentation and method: We present two unrelated cases of pubertal virilization due to NR5A1/SF-1 gene mutation. Both were suspected to be primarily affected by 5-alph...

Background: In recent years, traumatic brain injury (TBI) has been identified as a significant cause of pituitary dysfunction in children. Paediatric prospective studies are rare especially for mild TBI.Objective and hypotheses: The aim of this present study was to evaluate the frequency of hypopituitarism after mild, moderate and severe TBI in hospitalized children, and determining factors of this deficiency.Method: A prospective ...

Background: Newborn screening for congenital adrenal hyperplasia (CAH) has been shown to reduce time to diagnosis, and thus morbidity and mortality. Internationally, newborn screening for CAH continues to expand and screening techniques have improved, with the implementation of second-tier testing and use of gestational age stratification. The aim of this study was to examine the incidence and spectrum of early clinical presentations of CAH in an unscreened po...