hrp0089mte2.1 | Endocrine Complications in Thalassaemia | ESPE2018

Endocrine Complications in Thalassaemia

Skordis Nicos

Multiple transfusions in patients with Thalassaemia Major (TM) result in iron overload, which accumulates in tissues with high levels of transferrin-receptors such liver, heart and endocrine glands The nature and frequency of endocrinopathies differ between countries because of the different levels of treatment followed by centres across the world.1. Short stature. The child with TM has a particular growth pattern, which is relatively no...

hrp0095p1-215 | Adrenals and HPA Axis | ESPE2022

Salt-Wasting CAH phenotype as a result of the TNXA/TNXB Chimera 1 (CAH-X CH-1) and the severe IVS2-13A/C>G in CYP21A2 gene

Fanis Pavlos , Skordis Nicos , A Phylactou Leonidas , Neocleous Vassos

Background: Genetic diversity of mutations in the CYP21A2 gene is the main cause of the monogenic Congenital adrenal hyperplasia (CAH) disorder. On chromosome 6p23.1, the CYP21A2 gene is partially overlapped by the TNXB gene and reside in tandem with their highly homologous corresponding pseudogenes (CYP21A1P and TNXA), which leads to recurrent homologous recombination.Methods and Results: The genetic s...

hrp0092rfc8.3 | Pituitary, Neuroendocrinology and Puberty Session 1 | ESPE2019

Central Precocious Puberty Caused by Novel Mutations in the Promoter and 5'-UTR Region of the Imprinted MKRN3 Gene

Fanis Pavlos , Skordis Nicos , Toumba Meropi , Papaioannou Nikoletta , Makris Anestis , Kyriakou Andreas , Neocleous Vassos , Phylactou Leonidas

Background: Central Precocious Puberty (CPP) is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. To date, mutations in the coding region of KISS1, KISS1R, DLK1 and MKRN3 genes have been reported as causative for CPP. This study investigated the presence of causative mutations in both the promoter and the 5'-UTR regions of the MKRN3 ...

hrp0092p2-275 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

46,XY Complete Gonadal Dysgenesis in a Familial Case with a Rare Mutation in the Desert Hedgehog (DHH) Gene

Neocleous Vassos , Fanis Pavlos , Cinarli Feride , Oulas Anastasios , Spyrou George M , Phylactou Leonidas A , Skordis Nicos

Purpose: Disorders of sex development (DSD) have been linked with gene defects that lead to gonadal dysgenesis. Herein, we aimed at identifying the genetic cause of gonadal dysgenesis in a patient with primary amenorrhoea and 46,XY karyotype from a consanguineous family.Methods and Results: Whole exome sequencing (WES) was performed and revealed in homozygosity the rare and only once reported p.Arg164Pro missense mutatio...

hrp0084p2-338 | Fat | ESPE2015

A Novel Melanocortin-4-Receptor Gene Mutation Associated with Early Onset Severe Obesity

Toumba Meropi , Shammas Christos , Neocleous Vassos , Phelan Marie , Skordis Nicos , Phylactou Leonidas , Mantzoros Christos

Background: The melanocortin-4-receptor gene (MC4R) is a key regulator for appetite and satiety. MC4R mutations account for 6–8% of severe obesity in children with variable expression and penetrance.Case presentation: A 3-year-old girl is presented with severe early onset and progressive obesity. She was born full-term with appropriate of gestational age weight by non-consanguineous parents. She had normal psychomotor milestones an...

hrp0095p1-270 | Fat, Metabolism and Obesity | ESPE2022

Homology modelling analysis provides insight into ADCY3, a candidate obesity gene

Toumba Meropi , Fanis Pavlos , Neocleous Vassos , Vlachakis Dimitrios , Phylactou Leonidas , Skordis Nicos , Mantzoros Christos , Pantelidou Maria

Background: In an effort to better understand the molecular basis of obesity, studies focus on genetic loci mapping to the leptin–melanocortin pathway, one of the key mechanisms for controlling food intake and body weight. Adenylate cyclase 3 (ADCY3) is a key genetic candidate as it seems to have an essential role at primary neuronal cilia in regulating body weight. We have previously reported the novel probably pathogenic ADCY3</em...

hrp0095p1-562 | Pituitary, Neuroendocrinology and Puberty | ESPE2022

DNA methylation status of MKRN3 in puberty: studies in Central Precocious Puberty girls and in pubertal mouse

Fanis Pavlos , Morrou Maria , Tomazou Marios , Toumba Meropi , Neocleous Vassos , Skordis Nicos , A Phylactou Leonidas

Background: Makorin RING finger protein 3 (MKRN3) is an important factor located on chromosome 15 in the imprinting Prader-Willi syndrome - associated region. Imprinted MKRN3 expressed in hypothalamic regions essential for puberty initiation and mutations have been found in patients with central precocious puberty (CPP). CPP caused by the early activation of pulsatile Gonadotropin releasing hormone (GnRH) secretion is clinically defined by the early maturation...

hrp0092p1-334 | Fat, Metabolism and Obesity (2) | ESPE2019

ADCY3 Genetic Variants in Cypriot Obese Children

Frixou Maria , Fanis Pavlos , Skordis Nicos , Stylianou Charilaos , Tanteles George A , Toumba Meropi , Neocleous Vassos , Phylactou Leonidas A , Pantelidou Maria

Background: The adenylate cyclase 3 (ADCY3) gene encodes a membrane-associated protein involved in the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). This gene seems to be is involved in the regulation of several metabolic processes and has been recently associated to pathophysiological metabolic conditions. Several ADCY3 variants have been linked with obesity in children.M...

hrp0089p2-p387 | Thyroid P2 | ESPE2018

Phenotype and Genotype of Four Patients with Thyroid Hormone Resistance Syndrome due to Mutations in the THRB Gene

Toumba Meropi , Neocleous Vassos , Fanis Pavlos , Skordis Nicos , Phylactou Leonidas A , Tanteles George A , Kyriakidou-Himonas Marinella , Picolos Michalis

Background: Resistance to thyroid hormone (RTH) is a dominantly inherited rare disorder (1:40000) mainly due to mutations in the THRB gene that lead to a decreased end-organ responsiveness to thyroid hormone. Clinical and molecular characteristics of four patients with RTH are described.Patients and methods: Four patients from three non-related families were studied; two boys (8.3 and 9.2 years old) and 2 adults (35 year old male and 27 year old...

hrp0086rfc12.5 | Neuroendocrinology | ESPE2016

A Novel MKRN3 Nonsense Mutation Causing Familial Central Precocious Puberty

Christoforidis Athanasios , Skordis Nicos , Fanis Pavlos , Dimitriadou Meropi , Sevastidou Maria , Phelan Marie M. , Neocleous Vassos , Phylactou Leonidas A.

Background: The onset of puberty is influenced by the interplay of stimulating and restraining factors, many of which have a genetic origin. Premature activation of the GnRH secretion in central precocious puberty (CPP) may arise either from gain-of-function mutations of the KISS1 and KISS1R genes or loss-of-function manner mutations of the MKRN3 gene leading to MKRN3 deficiency.Objective and hypotheses: Explore the genetic cau...