%A Stoupa,Athanasia %A Al Hage Chehade,Ghada %A Chaabane,Rim %A Kariyawasam,Dulanjalee %A Szinnai,Gabor %A Hanein,Sylvain %A Bole-Feysot,Christine %A Fourrage,Cécile %A Nitschke,Patrick %A Thalassinos,Caroline %A Pinto,Graziella %A Mnif,Mouna %A Baron,Sabine %A De Kerdanet,Marc %A Reynaud,Rachel %A Barat,Pascal %A Hachicha,Mongia %A Belguith,Neila %A Polak,Michel %A Carré,Aurore %D 2021 %J Frontiers in Endocrinology %C %F %G English %K Congenital Hypothyroidism,Dyshormonogenesis,mutations,Targeted-Next- generation sequencing,Gland in situ %Q %R 10.3389/fendo.2020.545339 %W %L %M %P %7 %8 2021-February-22 %9 Original Research %+ Michel Polak,INSERM U1016, Cochin Institute, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité,France,michel.polak@aphp.fr %+ Michel Polak,IMAGINE Institute affiliate,France,michel.polak@aphp.fr %+ Michel Polak,Pediatric Endocrinology, Gynecology and Diabetology Unit, Hôpital Universitaire Necker-Enfants Malades,France,michel.polak@aphp.fr %+ Michel Polak,Centre de Référence des Maladies Endocriniennes Rares de la Croissance et du Développement, Necker-Enfants Malades University Hospital,France,michel.polak@aphp.fr %+ Michel Polak,Centre Régional de Dépistage Néonatal (CRDN) Ile de France,France,michel.polak@aphp.fr %+ Aurore Carré,INSERM U1016, Cochin Institute, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité,France,michel.polak@aphp.fr %+ Aurore Carré,IMAGINE Institute affiliate,France,michel.polak@aphp.fr %# %! Genetic of Thyroid Dyshormonogenesis %* %< %T High Diagnostic Yield of Targeted Next-Generation Sequencing in a Cohort of Patients With Congenital Hypothyroidism Due to Dyshormonogenesis %U https://www.frontiersin.org/articles/10.3389/fendo.2020.545339 %V 11 %0 JOURNAL ARTICLE %@ 1664-2392 %X ObjectiveTo elucidate the molecular cause in a well-characterized cohort of patients with Congenital Hypothyroidism (CH) and Dyshormonogenesis (DH) by using targeted next-generation sequencing (TNGS).Study designWe studied 19 well-characterized patients diagnosed with CH and DH by targeted NGS including genes involved in thyroid hormone production. The pathogenicity of novel mutations was assessed based on in silico prediction tool results, functional studies when possible, variant location in important protein domains, and a review of the recent literature.ResultsTNGS with variant prioritization and detailed assessment identified likely disease-causing mutations in 10 patients (53%). Monogenic defects most often involved TG, followed by DUOXA2, DUOX2, and NIS and were usually homozygous or compound heterozygous. Our review shows the importance of the detailed phenotypic description of patients and accurate analysis of variants to provide a molecular diagnosis.ConclusionsIn a clinically well-characterized cohort, TNGS had a diagnostic yield of 53%, in accordance with previous studies using a similar strategy. TG mutations were the most common genetic defect. TNGS identified gene mutations causing DH, thereby providing a rapid and cost-effective genetic diagnosis in patients with CH due to DH.