hrp0098p2-230 | Pituitary, Neuroendocrinology and Puberty | ESPE2024

Advancing Endocrine Disorder Diagnosis in Cyprus: The Cyprus Institute of Neurology and Genetics as an ENDO-ERN Reference Center

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

This report provides an overview of the Molecular Genetics-Function and Therapy (MGFT) department's present and past activities at the Cyprus Institute of Neurology and Genetics (CING), serving as an affiliated Reference Center (RC) for the European Reference Network on Rare Endocrine Conditions (Endo-ERN). Over a period of more than 15 years, the MGFT department has collaborated extensively with endocrine specialists from local government hospitals and the private sector...

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...

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 ...

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...

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...

hrp0082p2-d2-282 | Adrenals &amp; HP Axis (1) | ESPE2014

Steroid 11β-Hydroxylase Deficiency Due to CYP11B1 Mutations in Females with Hyperandrogenemia

Shammas Christos , Byrou Stefania , Phedonos Alexia AP , Nicolaou Stella , Toumba Meropi , Skordis Nicos , Neocleous Vassos , Phylactou Leonidas A

Background: More than >90% of cases of congenital adrenal hyperplasia (CAH) are caused by 21-hydroxylase deficiency, steroid 11β-hydroxylase deficiency accounts for 5–8% of cases.Objective and hypotheses: To seek evidence on the prevalence of CYP11B1 mutations in prepubertal girls, adolescents and adult females with clinical signs of hyperandrogenemia.Method: The study included 31 girls with premature adrenar...

hrp0097rfc1.2 | Adrenals and HPA Axis | ESPE2023

The chimeric CYP21A1P/CYP21A2 and TNXA/TNXB gene deficiencies in patients with Congenital Adrenal Hyperplasia

Fanis Pavlos , Toumba Meropi , Katerina Chrysostomou Anna , Mousikou Maria , Nicolaou Stella , Kyriakou Andreas , Neocleous Vassos , A Phylactou Leonidas

Background: Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder with more than 90% of cases caused by defects in the steroid-21 hydroxylase (CYP21A2) gene. Such defects are the main cause of 21-hydroxylase enzyme deficiency that affects the biosynthesis of cortisol and aldosterone. The CYP21A2 gene is part of the RCCX module, which is located on chromosome 6p21.3, in the major histocompatibility complex (MHC) class III reg...

hrp0095p1-358 | Pituitary, Neuroendocrinology and Puberty | ESPE2022

Pathogenic and Low-Frequency genetic determinants in children with Central Precocious Puberty

Fanis Pavlos , Toumba Meropi , A Tanteles George , Iasonides Michalis , C Nicolaides Nicolas , Nicolaou Stella , Kyriakou Andreas , Neocleous Vassos , A Phylactou Leonidas , Skordis Nicos

Background: Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height as well as psychological consequences. So far only a limited number of genetic determinants have been associated with the pathogenesis in children with CPP. In this original research, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were i...