IMPE Abstracts

Introduction: Phaeochromocytomas and paragangliomas (PPGLs)are rare neuroendocrine tumors. The number of genetically determined PPGLs with specific variants rises to approximately 70%. The genetic status of patients with PPGLs is key for precision diagnosis, treatment and surveillance of affected patients and their families. Pathogenic gain-of-function variants in EPAS1gene, mainly as germline mosaicism or somatic mutations, cause its activation and l...

In patients with 46,XY disorders of sex development (DSD), next-generation sequencing (NGS) analysis leads to an aetiological diagnosis in ~40% of the cases. One contribution of this diagnostic approach is the possibility of applying reverse phenotyping when a variant in a gene associated with multiple organ hits is found. The aim of this work is to report a case of a patient with 46,XY DSD in whom the identification of a novel variant in MYRF led to the detection of a clinica...

Introduction: Acid-labile subunit (ALS) forms ternary complexes with insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) being essential for normal circulating IGF-1 levels. The IGFALS gene encodes the ALS and loss-of-function variants in IGFALS cause ALS deficiency, which has a prevalence < 1/1.000.000. These patients generally present with moderate short stature, extraordinarily low serum levels of IGF-I and IGFBP-3 ...

The genetic defects underlying hypogonadotrophic hypogonadism (HH) are known in approximately 50% of cases. In normosmic patients, abnormal GnRH production or action may be due to defects in regulatory factors or in the genes encoding GnRH or GnRHR. Although many gene variants have been described in GNRHR (4q13.2), the potential impact of structural alterations of the resulting mutant proteins have not been studied. In this study, we analysed the 3D-structure of the variant Gn...

Human growth is highly dependent on the GH-IGF-I axis. GH binding to GH receptor activates janus kinase 2 (JAK2)-signal transducer and activator of transcription 5b (STAT5b) pathway which stimulates transcription of IGF1, IGFBP3, and IGFALS. Although STAT5b deficiency was established as an autosomal recessive disorder, heterozygous dominant-negative STAT5B variants were reported in patients with less severe growth deficit and milder immune dysfunction. Our aim was to develop a...

Introduction: Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome caused by genetic or epigenetic defects within the chromosome 11p15.5 region. BWS growth pattern with accelerated growth during infancy is widely known, and whenever there is a change in the expected growth, further investigation is warranted.Objective: To describe a patient with BWS and growth failure.Case report:</s...

Introduction: MS-MLPA is a specific and sensitive technique for detecting copy number variants and methylation defects in the regions of interest associated with imprinting diseases as Beckwith-Wiedemann (BWS) and Silver Russell (SRS) syndromes and. Both are growth disorders associated with opposite molecular alterations in the 11p15.5 imprinting locus.Aim: To analyze the diagnostic efficiency of MS-MLPA in a cohort of p...

Introduction: SOFT syndrome (MIM#614813), denoting Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis, is a rare primordial dwarfism syndrome encompassing severe growth failure of prenatal onset, craniofacial dysmorphism, sparse hair, and digital abnormalities associated with biallelic pathogenic POC1Agene variants. Phenotypic spectrum has recently been expanded to include insulin resistance (IR) and muscle cramps.<p class="abst...

Introduction: Short Stature (SS), defined as height below -2 SD, is a common reason for referral to pediatric endocrinologists. Genetic factors determine ~80% of adult height. Lately, next-generation sequencing (NGS) has led to the discovery of an increasing number of novel monogenic causes for SS.Objective: The aim of this work was to identify the genetic etiology of SS of unknown origin (SSUO) in children.<p class=...

Introduction: Silver-Russell Syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction, relative macrocephaly and protruding forehead in early life, body asymmetry and feeding difficulties. Although several genetic mechanisms that cause the syndrome are known, more than 40% of patients with an SRS-like phenotype remains without an etiological diagnosis. In the last few years, clinical reports have suggested that single...