ESPE Abstracts

Background: Idiopathic central precocious puberty (ICPP) results from the premature reactivation of the hypothalamic-pituitary-gonadal axis leading to development of secondary sexual characteristics prior to 8 years in girls or 9 years in boys. Mutations in the maternally imprinted MKNR3 gene are the most common identified genetic cause of ICPP to date. Expression of MKRN3 in the arcuate nucleus is presumed to be inhibitory to GnRH secretion, but the exact mechanism remains un...

Background: Proopiomelanocortin (POMC) deficiency is characterised clinically by adrenal insufficiency, obesity and red hair. As a rule, such patients present early in life with severe hypoglycemia, which leads to initiation of glucocorticoid therapy. We describe here a case of POMC deficiency, where adrenal insufficiency was not diagnosed until the fourth year of life.Objective and hypotheses: To present a case of late diagnosis of POMC deficiency and c...

Background: An accurate and comprehensive assessment of steroid hormones is pivotal for differential diagnosis of disorders of sex development (DSD) 46,XY, a part of which may be due to defects of testosterone biosynthesis.Objective and hypotheses: To describe and characterise a case of DSD 46,XY presented with unusual serum steroid profile.Method: Serum steroid hormones were analysed by liquid chromatography-tandem mass spectromet...

Background: SHOX encodes a transcription factor implicated in skeletal development. Approximately 70% and ~2.5% of Leri-Weill dyschondrosteosis (LWD) and idiopathic short stature (ISS) patients, respectively, have a defect in SHOX or its regulatory regions.Objective and hypotheses: i) To perform SHOX mutation screening in a cohort of 585 patients referred with a clinical suspicion of LWD or ISS. ii) To determine which is the <e...

Background: Homozygous aggrecan (ACAN) mutations have been described in a few skeletal dysplasias whilst more recently, heterozygous ACAN mutations have been reported in few families presenting with idiopathic short stature with advanced bone maturation and premature growth cessation.Case presentation: We describe two novel heterozygous ACAN stop mutations, detected using a skeletal dysplasia NGS panel and confirmed by Sanger sequencing...

Background: The pituitary set-point for TSH synthesis and secretion is known to be an individual parameter with a strong genetic influence. Type II iodothyronine deiodinase is a pituitary enzyme involved in local deiodination of T4 and negative feed-back loop for TSH secretion. Defects in DIO2 have not been reported in humans; however, Dio2 knockout mouse has pituitary resistance to T4 with elevated TSH, T4 and TSH/T4 ratio, with nor...

Background: Studies about the genetics of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) in Chinese children are less.Objective and hypotheses: Study the genotypes of Chinese probands with salt-wasting form of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CAH) and performed pedigree-based linkage analysis.Method: We have performed genetic-testing (Method...

Background: Congenital hyperinsulinism (CHI) is the most common cause of the persistent hypoglycemia in children. Mutations in KCNJ11 and ABCC8 genes coding potassium channel subunits are responsible for a significant proportion of CHI patients. The type of mutation correlates with the type of B-cell hyperplasia (focal or diffuse), and determinates further diagnostics, treatment and prognosis of disorder.Aims and objectives: The aim of ...

Background: Mexico is globally ranked as one of the countries with the highest incidence of congenital hypothyroidism. There are few studies that have searched for germinal mutations of candidate genes, such as NKX2-1, in patients with congenital hypothyroidism.Objective and hypotheses: i) To search for NKX2-1 mutations in blood samples of patients with confirmatory diagnosis of congenital hypothyroidism (CH) due to thyroid dysgenesis (...

Background: Primary ovarian failure (POF) is a major cause of female infertility. POF is characterized by amenorrhea, hypo-estrogenism, and elevated gonadotrophin levels. In POF disorder, several genetic alterations have been described, however in most of the patients the etiology of this disorder remains unknown.Objective and hypotheses: To identify new genes implicated in the development of POF using whole-exome sequencing (WES)....