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...

hrp0082p2-d2-282 | Adrenals & 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...

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...

hrp0089fc13.1 | Pituitary, Neuroendocrinology and Puberty 2 | ESPE2018

Molecular Screening of Genes Associated with Central Precocious Puberty

Fanis Pavlos , Neocleous Vassos , Toumba Meropi , Gorka Barbara , Stylianou Charilaos , Galli-Tsinopoulou Assimina , Nicolaou Stella , Kyriakou Andreas , Dimitriadou Meropi , Christoforidis Athanasios , Skordis Nicos , Phylactou Leonidas A

Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis through the activation of the gonadotropin releasing hormone (GnRH). Gain-of-function mutations of the KISS1 and KISS1R genes or loss-of-function mutations of the makorin RING-finger protein 3 (MKRN3) have been linked with CPP. Moreover intronic and intragenic variants harbouring the imprinted loci of MKRN3-MAGEL2 and DLK1 g...

hrp0086p1-p730 | Pituitary and Neuroendocrinology P1 | ESPE2016

MKRN3 Mutations and Central Precocious Puberty

Neocleous Vassos , Toumba Meropi , Sevastidou Maria , Phelan Marie M , Shammas Christos , Nicolaou Stella , Stylianou Charilaos , Christoforidis Athanasios , Fanis Pavlos , Phylactou Leonidas A , Skordis Nicos

Background: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis and increasing evidence suggests a genetic origin. Premature activation of the GnRH secretion in 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: To identify loss-of-...

hrp0092p1-394 | Pituitary, Neuroendocrinology and Puberty (2) | ESPE2019

Next Generation Sequencing in GnRH Deficient Patients with Congenital Hypogonadotrophic Hypogonadism: Novel Findings in KAL1, SRA1, WDR11, FGFR1, CHD7 and PROP1 Genes

Neocleous Vassos , Fanis Pavlos , Toumba Meropi , Cinarli Feride , Schiza Melpo , Stylianou Charilaos , Tanteles George A , Oulas Anastasios , Spyrou George M , Skordis Nicos , Phylactou Leonidas A

Abstract: Objective: Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disease caused by GnRH deficiency and characterized by absent or incomplete puberty with infertility. The identification of the genetic cause in this group of patients through the use of next generation sequencing (NGS) can assist to the clinical management.Methods: Seven GnRH deficient nonrelated Cypriot probands were ...

hrp0089p2-p016 | Adrenals and HPA Axis P2 | ESPE2018

The Spectrum of Genetic Defects in Congenital Adrenal Hyperplasia in the Population of Cyprus: A Retrospective Analysis

Skordis Nicos , Fanis Pavlos , Toumba Meropi , Stylianou Charilaos , Picolos Michalis , Andreou Elena , Kyriakou Andreas , Yiannakide-Myli Lambrini , Iasonides Michalis , Nicolaou Stella , C Kyriakides Tassos , Tanteles George A , Neocleous Vassos , Phylactou Leonidas A

Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is worldwide the most common autosomal recessive disorder caused by defects in the CYP21A2 gene.Objective: The main objective of the study was to evaluate CAH in Cyprus over a 10 year period.Methods: All known patients were included in a population retrospective subset analysis of Cypriot patients with confirmed CAH and their clinica...

hrp0092p1-166 | Adrenals and HPA Axis (1) | ESPE2019

Cortisol levels in glucagon stimulation tests in children evaluating for short stature: clinical and laboratorial correlations

Maliachova Olga , Triantafyllou Panagiota , Slavakis Aris , Dimitriadou Meropi , Christoforidis Athanasios

Background: Glucagon stimulation test (GST) is used to assess growth hormone (GH) and cortisol reserves in children being investigated for GH deficiency, as a small percentage of children with idiopathic GH deficiency can also exhibit deficiency in the adrenocorticotrophic hormone (ACTH)-cortisol axis. However, the extent of normal cortisol response after glucagon stimulation and its associations with clinical and laboratory parameters have not been thoroughly...