hrp0086fc11.2 | Thyroid | ESPE2016

Overexpression of DYRK1A Located in the Down Syndrome Critical Region, Leads to Primary Hypothyroidism in Down Syndrome through Interaction with FOXE1

Kariyawasam Dulanjalee , Carre Aurore , Rachdi Latif , Polak Michel

Background: Down Syndrome (DS) patients have a higher incidence of primary hypothyroidism. We previously demonstrated that transgenic mice overexpressing Dyrk1A had developmental (larger primary thyroids at E15.5 stage of development), morphological (disorganized follicles) and functional (significant lower plasma T4) impairments similar to DS thyroidal impairments (Endocrinology 2015). DYRK1A, localized in the DS critical region on chromosome 21, is therefore the can...

hrp0089fc5.2 | Thyroid | ESPE2018

Enrichment of Inherited Rare Variants in Non-Syndromic Congenital Hypothyroidism from Thyroid Dysgenesis Identified By Exome Sequencing: the Contribution of IKBKE to Vasculogenesis and Thyroid Development

Larrivee-Vanier Stephanie , Magne Fabien , Jean-Louis Martineau , Carre Aurore , Bui Helen , Samuels Mark E. , Polak Michel , Van Vliet Guy , Deladoey Johnny

Congenital hypothyroidism from thyroid dysgenesis (CHTD) is mainly a sporadic and non-syndromic condition occurring in 1:4,500 live births. In contrast to rare cases of syndromic monogenic CHTD, non-syndromic (NS) CHTD shows low familial recurrence risk (~2%) and low concordance rate between MZ twins, suggesting a two-hit scenario combining post-zygotic events with either a de novo monogenic mutation or incomplete penetrance of polygenic inherited variants,. As this l...

hrp0086fc11.3 | Thyroid | ESPE2016

Genetic Heterogeneity Revealed by WES in a Cohort of Patients with Brain-Lung-Thyroid Syndrome

Stoupa Athanasia , Kariyawasam Dulanjalee , Gueriouz Manelle , Malan Valerie , Fanen Pascale , Nitschke Patrick , Zarhrate Mohammed , Bole-Feysot Christine , Besmond Claude , Polak Michel , Carre Aurore

Background: Brain-Lung-Thyroid (BLT) syndrome (OMIM# 610978) is characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS), and benign hereditary chorea and is caused by thyroid transcription factor 1 (NKX2-1/TTF1) haploinsufficiency. The phenotype can be partial or complete and there is a large phenotypic variability.Objectives and hypotheses: Identify new genes in a selected group of patients presenting thyroi...

hrp0094fc10.4 | Thyroid | ESPE2021

Towards a novel genetic model for Congenital Hypothyroidism due to thyroid dysgenesis

Stoupa Athanasia , Jabot-Hanin Fabienne , Kariyawasam Dulanjalee , Quoc Adrien NGuyen , Hanein Sylvain , Bole-Feysot Christine , Nitschke Patrick , Polak Michel , Carre Aurore ,

Background: Congenital hypothyroidism (CH) affects one in 3000 children at birth. In 65% of cases, CH is due to thyroid dysgenesis (CHDT). For CHDT, there is a family component and therefore genetic. Over the past 20 years, disease-causing mutations in 10 genes have been implicated in CHDT cases (NKX2-1/TTF1, FOXE1/TTF2, NKX2-5, PAX8, GLIS3, NTN1/Netrin-1, JAG1, BOREALIN/CDCA8, TUBB1</...

hrp0094p1-193 | Thyroid B | ESPE2021

Further evidence that Borealin/CDCA8 is involved in thyroid morphogenesis and aging

Didier-Mathon Hortense , Stoupa Athanasia , Karyiawasam Dulanjalee , Yde Sonny , Cagnard Nicolas , Nitschke Patrick , Scharfmann Raphael , Luton Dominique , Polak Michel , Carre Aurore ,

Background: We found BOREALIN/CDCA8 mutations in patients with Congenital Hypothyroidism and Thyroid Dysgenesis, varying from asymmetric lobes to athyreosis (Carré et al. Hum Mol Genet 2017). Borealin is a major component of the Chromosomal Passenger Complex, an essential regulator of mitosis. We demonstrated a new feature of BOREALIN: involvement in the adhesion and the migration of the thyrocytes.<strong...

hrp0086ha2 | BOREALIN Mutations in Thyroid Dysgenesis Reveal a New Function of this Protein in Cell Adhesion and Migration | ESPE2016

BOREALIN Mutations in Thyroid Dysgenesis Reveal a New Function of this Protein in Cell Adhesion and Migration

Carre Aurore , Stoupa Athanasia , Karyiawasam Dulanjalee , Gueriouz Manelle , Ramond Cyrille , Gaujoux Sebastien , Glaser Nicolas , Leger Juliane , Zenaty Delphine , Nitschke Patrick , Bole-Feysot Christine , Parisot Melanie , Hubert Laurence , Scharfmann Raphael , Munnich Arnold , Besmond Claude , Taylor William , Polak Michel

Background: Congenital hypothyroidism is primarily due to thyroid dysgenesis (TD). The genes implicated in TD, account for a small number of patients with monogenic forms, less than 5%. Borealin is a major component of the Chromosomal Passenger Complex, an essential regulator of mitosis.Objective and hypotheses: To understand the role of Borealin mutations found in patients with TD.Method: We performed whole exome sequencing (WES) ...

hrp0089fc5.1 | Thyroid | ESPE2018

Beta1-Tubulin Gene (TUBB1) Mutations Cause Thyroid Dysgenesis Associated to Abnormal Platelet Morphology and Hyper-Aggregation

Carre Aurore , Stoupa Athanasia , Adam Frederic , Kariyawasam Dulanjalee , Strassel Catherine , Gawade Sanjay , Szinnai Gabor , Kauskot Alexandre , Lasne Dominique , Janke Carsten , Natarajan Kathiresan , Schmitt Alain , Bole-Feysot Christine , Nitschke Patrick , Leger Juliane , Jabot-Hanin Fabienne , Tores Frederic , Michel Anita , Munnich Arnold , Besmond Claude , Scharfmann Raphael , Lanza Francois , Borgel Delphine , Polak Michel , Federation Parisienne pour le Depistage et la Prevention des Handicaps de l'Enfant FPDPHE Michel

Background: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, with an incidence of 1:3000 neonates, and one of the most frequent preventable causes of mental retardation worldwide. Most (65%) cases of primary permanent CH are due to thyroid dysgenesis (TD). However, a genetic cause is identified in less than 5% of CH due to DT.Methods: We performed WES (Whole Exome Sequencing) for siblings with childhood-onset TD and we analy...