ESPE Abstracts (2021) 94 FC10.3

ESPE2021 Free Communications Thyroid (6 abstracts)

Genetic analyses in patients having congenital hypothyroidism with gland-in-situ by next-generation sequencing

Lucie Levaillant 1,2 , Natacha Bouhours-Nouet 1,2 , Frédéric Illouz 2,3 , Nathalie Bouzamondo 2,5 , Patrice Rodien 2,3 , Delphine Prunier-Mirebeau 2,5 & Régis Coutant 1,2


1Department of Pediatric Endocrinology and Diabetology, University Hospital of Angers, Angers, France.;2Reference Center for Rare Diseases of Thyroid and Hormone Receptivity, University Hospital of Angers, Angers, France.;3Department of Endocrinology, Diabetes and Nutrition, University Hospital of Angers, Angers, France.;4Members of the Congenital hypothyroidism with gland-in-situ study group: Jessica Amsellem Jager, Anne Bachelot, Pascal Barat, Sabine Baron, Candace Bensignor, Aude Brac De La Perriere, Yasmine Braik Djellas, Morgane Caillot, Emmanuelle Caldagues, Marie-Neige Campas, Marylène Caquard, Audrey Cartault, Julie Cheignon, Anne Decrequy, Brigitte Delemer, Katherine Dieckmann, Aurélie Donzeau, Emilie Doye, Melanie Fradin, Mélanie Gaudillière, Frédérique Gatelais, Magali Gorce, Isabelle Hazart, Nada Houcinat, Laure Houdon, Marielle Ister-Salome, Lucie Jozwiak, Patrick Jeannoel, Francois Labarthe, Didier Lacombe, Anne-Sophie Lambert, Christine Lefevre, Bruno Leheup, Clara Leroy, Benedicte Maisonneuve, Isis Marchand, Emeline Marquant, Matthias Muszlak, Letitia Pantalone, Sandra Pochelu, Dr Chloé Quelin, Catherine Radet, Peggy Renoult-Pierre, Rachel Reynaud, Stéphanie Rouleau, Cécile Teinturier, Julien Thevenon, Caroline Turlotte, Aline Valle, Melody Vierge, Carine Villanueva, Alban Ziegler.;5Genetics and Biochemistry Department, University Hospital of Angers, Angers, France


Introduction: Primary Congenital Hypothyroidism (CH) is an abnormal function of the thyroid gland present at birth. Anomalies of thyroid function are usually classified between thyroid dysgenesis, corresponding to an abnormal embryological development of the thyroid, and CH with gland-in-situ (GIS), resulting from mutations in genes involved in thyroid hormone synthesis. We report 105 patients with CH with GIS that have been referred to Angers University Hospital reference center for rare diseases of thyroid and hormone receptivity for genetic testing by next-generation sequencing (NGS).

Methods: 105 patients having a CH with GIS had a NGS containing 48 genes involved in thyroid development and metabolism, including DUOX1, DUOXA1, DUOX2, DUOXA2, FOXE1, GNAS, HHEX, IYD, NKX2-1, NKX2-5, PAX8, SLC26A4 (Pendrin), SLC5A5 (NIS), TBX1, TG, TPO, and TSHR. Patients were sorted in resolved, probably resolved or partially resolved genetic cases according to the gene involved (recessive or dominant), the classification of variants (pathogenic, likely pathogenic or of uncertain significance according the guidelines of the American College of Medical Genetics) and the potential familial segregation.

Results: Genetic testing identified 99 variants in 10 genes: DUOXA1, DUOX2, DUOXA2, NKX2-1, PAX8, SLC26A4, SLC5A5, TG, TPO and TSHR. These variants allowed to solve 29 genetic cases (28%), to have a probable resolution for 20 of them (19%) and to partially solve 22 cases (21%). Among patients having a neonatal TSH ≥ 100 mIU/L (n = 23), 74% were probably solved or solved cases, whereas when TSH was < 40 mIU/L (n = 28), only 5 patients (18%) were probably solved or solved cases. Eight patients carrying heterozygous variants on 2 different genes, they were categorized as partially solved cases (digenism ?).

Conclusion: We can recommend NGS sequencing for every patient having CH with GIS. The study of environmental factors would be interesting in CH with GIS having neonatal TSH < 40 mIU/L. The transient or permanent nature of these CH remains to be established.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

Online,
22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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