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...

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...

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...

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 ...

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-...