ESPE Abstracts

Congenital hypothyroidism from thyroid dysgenesis (CHTD) is mainly a sporadic and non-syndromic condition occurring in 1:4,500 live births. In contrast to rare cases of syndromic monogenic CHTD, non-syndromic (NS) CHTD shows low familial recurrence risk (~2%) and low concordance rate between MZ twins, suggesting a two-hit scenario combining post-zygotic events with either a de novo monogenic mutation or incomplete penetrance of polygenic inherited variants,. As this l...

Introduction: Congenital multiple pituitary hormone deficiency (CMPHD) is a clinical condition that manifests in the early years of life. In most cases, pituitary stalk interruption syndrome (PSIS) can be detected by MR imaging. The current study presents a case with a novel candidate pathogenic gene Semaphorin 3A (SEMA3A) in CMPHD by whole-exome sequencing (WES).Materials and Methods: Genomic DNA was extracted from the ...

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: Approximately 10% of children born small for gestational age (SGA) fail to catch-up nd remain short (SGA-SS). Although several mechanisms causing SGA-SS have been elucidated, the primary cause remains speculative in most cases.Aim: To decipher genetic causes of SGA-SS defined as birth length and/or birth weight <-2 SD for gestational age, and body height <-2.5 SD after the 3rd year of life within a larg...

Differences of sex development (DSD) occurs when the development of chromosomal sex, gonadal or internal/external genitalia is atypical. It has an incidence of 1: 1000-4500 live born children. New chromosomal array technologies (SNP-array) can analyze the genome of the individual providing information of copy number variation (CNV) of specific chromosomal regions helping to identified pathogenic variants that could explain the etiology of the DSD. This study aims to analyze th...

GLI2 is a downstream transcription factor in Sonic Hedgehog signaling, acting early in ventral forebrain and pituitary development. Heterozygous GLI2 mutations have been reported in patients with isolated or combined pituitary hormone deficiency (CPHD).Objective: Study of genetic etiology of the hypopituitarism and identification of the genetic alteration in GLI2 gene.Methodology: Molecular study: Search for varia...

Background: Loss-of-function variants in the NR5A1 gene are frequent causes of 46,XY differences of sex development (DSD). To date, the Human Gene Mutation Database contains 291 NR5A1 variants, most of which are missense (69%). Mouse models demonstrated the effect of loss of SF-1 on sex development, but the interactome of SF-1 is huge and an explanation for the broad phenotype is still missing. Controversies exist as: a) in vitro transactivation assays of NR5A...

Background: Heterozygous loss-of-function mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with advanced bone age, early-onset osteoarthritis and intervertebral disc disease (SSOAOD; OMIM#165800). ACAN mutations is a relatively common finding in idiopathic short stature (ISS) and has been reported to be the cause of growth failure in approximately 2% of children with ISS. However, the underlying cellular and molecular mechanisms by ...

Introduction: Ovary development was once considered a largely passive process. RNA sequencing (RNAseq) approaches have allowed us to begin to characterise ovary development in previously unparalleled detail, revealing the process to be complex and, still, little understood. A challenge is synthesising and using these data to advance our understanding of clinical disease. Through a clinically-focused lens, we elucidate novel aspects of the transcriptional lands...

Background: Costello syndrome is a rare congenital disorder with characteristic findings involving multiple organ systems. The Costello Syndrome Family Network estimates that the birth prevalence in the United Kingdom is at least 1/500,000. So far, there has been only one affected individual reported in China.Objective and hypotheses: Diagnose the case of autosomal dominant Costello syndrome by direct squencing of HRAS gene. Analyze the correlation betwe...