ESPE Abstracts

Background: Basal levels of androgens, in particular 17-OHprogesterone (17OHP), are widely debated as predictors of non-classical congenital adrenal hyperplasia (NCCAH) among patients with precocious pubarche (PP). So many authors suggested the execution of ACTH stimulation test in all children with PP. The aim of our study was to identify clinical and biochemical predictors of NCCAH in children with PP.Methods: We conducted a prospective study of 92 pat...

Background: Central precocious puberty (CPP) is often familial but its genetic cause is largely unknown. Very recently, the makorin RING finger protein 3 (MKRN3) gene has been found mutated for the first time in 5 families with familial precocious puberty. The inheritance pattern is particular being the MKRN3 a maternal imprinted gene. Moreover in a recent genome wide association study common intronic or intragenic variants harbouring this gene and other two imprinted genes, D...

Background: Circadian disorganization of feeding behavior evoked by high fat diet (HFD) intake is suggested to be involved in the resulting weight gain and development of associated metabolic alterations and hypothalamic inflammation.Hypothesis: We hypothesized that this circadian alteration might be a consequence of rapid de-synchronization of different gene clusters relevant for metabolic control.Methods: We analyzed the circadia...

Prader–Willi syndrome (PWS) is a rare genetic disorder resulting from lack of expression of the paternally derived chromosome 15q11–13, associated with several complications, including pubertal disorders, short stature, hyperphagia, obesity, glucose metabolism abnormalities, scoliosis, obstructive sleep apnea syndrome (OSAS) and behavioral problems. We report the case of a girl affected by PWS who presented at the age of 5.9 with premature pubarche, accelerated lin...

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: Genetic causes of central precocious puberty (CPP) has been increasingly recognized, extending our knowledge of the triggering factors of human pubertal timing. Distinct etiologies remain to be elucidated in sporadic and familial cases. Methyl-CpG-binding protein 2 (MECP2) is a chromatin-associated protein that can activate or repress gene transcription, playing a role in neuronal maturation. It is encoded by MECP2 gene located at chromoso...

Background: Most published studies on 46,XY DSD focused on genetic findings without association with biochemical work-up.Objectives: To retrospectively analyze the clinical and genetic findings of a large cohort of 46,XY DSD patients.Methods: 285 non-syndromic 46,XY DSD individuals (192 sporadic and 89 familial cases) were studied. LH, FSH, testosterone (T), androstenedione (A) wer...

Background: Several genetic defects (GHR, SHOX, GHSR, NPR2, IGFALS) have been reported in children classified as ISS. ISS children are GH sufficient and about one third of them show low IGF-I levels, suggesting some degree of GH insensitivity.Objective: To explore potential genetic defects in ISS children suspicious of GH insensitivity, selected by low IGF-I levels and low response to IGF generation test.<...

Background: Human IGF1 gene defects are characterized by intrauterine and postnatal growth retardation, sensorineural deafness, microcephaly and intellectual disability. Seven cases have been reported so far, and the underlying pathophysiology has been characterized in only three.Objective: To describe a patient with severe short stature presenting a novel homozygous IGF1 gene mutation and its underlying pathogenic mechanism.<p clas...

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...