hrp0086rfc12.2 | Neuroendocrinology | ESPE2016

A Novel Mutation of KISS1R Causing a Normosmic Isolated Hypogonadotropic Hypogonadism

Yoshii Keisuke , Hugon-Rodin Justine , Gompel Anne , de Roux Nicolas

Background: Loss of function mutations in KISS1R, which encodes kisspeptin receptor have been reported in very few patients with normosmic isolated hypogonadotropic hypogonadism (nIHH).Objective and hypotheses: To describe the phenotype of the nIHH female patient with a novel homozygous KISS1R mutation and to characterize functionally this mutation. The patient was a 28 year-old Senegalese woman with primary amenorrhea. She was the seco...

hrp0082p1-d2-213 | Reproduction (1) | ESPE2014

The Association of Moebius Syndrome and Kallman Syndrome is Due to a Specific Mutation of TUBB3

Amouyal Melanie , Bouvagnet Patrice , Rochette Galliane , de Roux Nicolas

Background: Between the 6000 monogenic disorders, only few are due to a single mutation. Recently, a specific mutation has been described in TUBB3, encoding tubulin beta 3, in the association of Moebius syndrome (MS) and Kallmann syndrome (KS). MS is a congenital paralysis of eye and face’s muscles and can be caused by mutations of TUBB3. KS combines hypogonadotropic hypogonadism and anosmia.Objective and hypotheses: The combination of these two syn...

hrp0084fc-lb-2 | Late Breaking Abstracts | ESPE2015

Loss of Neuronal Dmxl2 Impairs the Maturation and the Activation of GnRH Neurons: a New Mechanism of GnRH Deficiency

Harbulot Carole , Tata Brooke , Jacquier Sandrine , De Roux Nicolas

Background: DMXL2 haploinsufficiency in humans was recently shown to cause the polyendocrine-polyneuropathia syndrome including a GnRH deficiency (OMIM #616113). The neuronal deletion of Dmxl2 in mice (Nes::Cre;Dmxl2loxp/wt) caused infertility and gonadotropic deficiency (Plos Biology 9 e1001952, 2014). Dmxl2 encodes rabconnectin-3α (rbcn-3α), which participates in the control of the V-ATPase activity an...

hrp0094p1-188 | Pituitary B | ESPE2021

Congenital hypogonadotropic hypogonadism in a large French cohort : New genetic findings

Talbi Abir , Hypogonadotropic Hypogonadism Study Group , de Roux Nicolas ,

Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by a dysfunction of the GnRH Axis. The clinical variability of the disease is accompanied by genetic heterogeneity. Indeed, more than 40 genes are implicated in the pathogenesis of this condition. The main goal of this present study was to characterize genetic defects in a large cohort of French CHH patients using a targeted NGS panel.Patients: a cohort of 120 unrelated patients (7...

hrp0092p2-251 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

3β-HSD2 Deficiency Due to Compound Heterozygosity of a Missense Mutation (p.Thr259Met) and a Frameshift Deletion (p.Lys273ArgFs*7) in an Under-Virilized Infant Male with Salt Wasting

Leka-Emiri Sofia , Taibi Ludmia , Fotinou Aspasia , Vlachopapadopoulou Elpis , Michalacos Stefanos , de Roux Nicolas

Objectives: To describe clinical, hormonal and genetic findings of an under-virilized infant male, 13 month old, of afghani origin, presented at the emergency department with salt-wasting adrenal crisis.Case report: The patient, a 13 month old male infant, presented at the emergency department with complaints of vomiting and fever. Physical examination was significant for severe dehydration along with perineal hypospadia...

hrp0089fc13.4 | Pituitary, Neuroendocrinology and Puberty 2 | ESPE2018

The Kallman Syndrome Gene Product is Specifically Expressed in ACTH-Expressing Cells and Dysplays Sexual Dimorphism Expression in Human Fetal Pituitary

Guimiot Fabien , Bonnard Adeline , Soussi-Yaniscostas Nadia , Schnoll Carol , de Roux Nicolas

Kallman syndrome is defined by the association of anosmia due to an agenesis of the olfactory bulbs and hypogonadotropic hypogonadism due to a GnRH deficiency which is currently explained by a deficit of GnRH neuron migration from the olfactory placode toward the hypothalamus. In fact, the X-linked form of KS is due to loss of function mutations in ANOS1 which encodes an extracellular protein (ANOSMIN) interacting with cell membrane heparin sulfate proteoglycans but a...

hrp0086fc12.1 | Neuroendocrinology | ESPE2016

Rabconnectin3-α is Indispensable for the Activation and Maturation of the GnRH Neuronal Network

Tata Brooke , Harbulot Carole , Csaba Zsolt , Jacquier Sandrine , de Roux Nicolas

Background: Acquisition and maintenance of fertility in mammals rely on the function of Gonadotropin Releasing Hormone (GnRH) neurons. During the juvenile period, GnRH neurons undergo morphological maturation, which involves changes in synaptic inputs and neuropeptide activation from afferent neurons. The functional importance of this maturation could be a pre-requisite for puberty onset. However, the mechanisms behind these dynamic changes have yet to be identified.<p cla...

hrp0092rfc15.6 | Late Breaking Abstracts | ESPE2019

Absence of Puberty and Estrogen Resistance by Estrogen Alpha Receptor Inactivation in Two Sisters: A Mutation for Variable Phenotypic Severity

Delcour Clémence , Khawaja Nahla , Mammeri Hedi , Drira Leila , Chevenne Didier , Ajlouni Kamel , De Roux Nicolas

Introduction: Estrogens play an essential role in reproduction and their peripheral action is mediated via nuclear alfa and beta receptors (ER) as well as membrane receptors. To date, only 3 females and 2 males from 3 families with a loss of function of ERa have been reported. The phenotype in these families was strongly suggestive of an estrogen resistance with an absence of a complete puberty, a delay in epiphyseal maturation with high estradiol levels and e...

hrp0086fc12.5 | Neuroendocrinology | ESPE2016

Abnormal Corticospinal Tract Decussation in Kallmann Syndrome due to ANOS1 (KAL1) Mutations: An Explanation of the Mirror Movements Frequently Observed in These Patients

Gonzalez-Briceno Laura , Sonnet Emmanuel , Guimiot Fabien , Laquerriere Annie , Kerlan Veronique , Salem Douraied Ben , Gunczler Peter , de Roux Nicolas

Background: Mirror movements (MM) are frequently associated to Kallmann syndrome (KS). They are mainly observed in patients with ANOS1 (KAL1) mutations. MM have never been reported in ANOS1 mutated females. A defect in the contralateral inhibition of the pyramidal tract has been proposed as the mechanism of MM in KS but never demonstrated.Objective and hypotheses: To investigate the molecular mechanism of a familial case of gonadotropic deficiency in whi...

hrp0089rfc9.5 | Pituitary, Neuroendocrinology and Puberty 1 | ESPE2018

Non-Isolated Central Precocious Puberty: Prevalence of Brain Lesions and Other Associated Disorders

Wannes Selmen , El Maleh Monique , De Roux Nicolas , Zenaty Delphine , Simon Dominique , Martinerie Laetitia , Storey Caroline , Gelwane Georges , Paulsen Anne , Ecosse Emmanuel , Jean-claude Carel , Juliane Leger

Background: Non-idiopathic central precocious puberty (CPP) is caused by acquired or congenital hypothalamic lesions visible on magnetic resonance imaging (MRI), or associated with various complex genetic and/or syndromic disorders without visible lesions on MRI. We investigated the different types and prevalences of non-isolated CPP phenotypes in a large group of consecutive patients with CPP.Methods: This observational cohort study included all patient...