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04-05-2022 | Goiter | Original Article

Mutational screening of the TPO and DUOX2 genes in Argentinian children with congenital hypothyroidism due to thyroid dyshormonogenesis

Authors: Maricel F. Molina, Patricia Papendieck, Gabriela Sobrero, Viviana A. Balbi, Fiorella S. Belforte, Elena Bueno Martínez, Ezequiela Adrover, María C. Olcese, Ana Chiesa, Mirta B. Miras, Verónica G. González, Mauricio Gomes Pio, Rogelio González-Sarmiento, Héctor M. Targovnik, Carina M. Rivolta

Published in: Endocrine | Issue 1/2022

Abstract

Purpose

Primary congenital hypothyroidism (CH) is the most common endocrine disease in children and one of the preventable causes of both cognitive and motor deficits. We present a genetic and bioinformatics investigation of rational clinical design in 17 Argentine patients suspected of CH due to thyroid dyshormonogenesis (TDH).

Methods

Next-Generation Sequencing approach was used to identify variants in Thyroid Peroxidase (TPO) and Dual Oxidase 2 (DUOX2) genes. A custom panel targeting 7 genes associated with TDH [(TPO), Iodothyrosine Deiodinase I (IYD), Solute Carrier Family 26 Member 4 (SLC26A4), Thyroglobulin (TG), DUOX2, Dual Oxidase Maturation Factor 2 (DUOXA2), Solute Carrier Family 5 Member 5 (SLC5A5)] and 4 associated with thyroid dysembryogenesis [PAX8, FOXE1, NKX2-1, Thyroid Stimulating Hormone Receptor (TSHR)] has been designed. Additionally, bioinformatic analysis and structural modeling were carried out to predict the disease-causing potential variants.

Results

Four novel variants have been identified, two in TPO: c.2749-2 A > C and c.2752_2753delAG, [p.Ser918Cysfs*62] and two variants in DUOX2 gene: c.425 C > G [p.Pro142Arg] and c.2695delC [p.Gln899Serfs*21]. Eighteen identified TPO, DUOX2 and IYD variants were previously described. We identified potentially pahogenic biallelic variants in TPO and DUOX2 in 7 and 2 patients, respectively. We also detected a potentially pathogenic monoallelic variant in TPO and DUOX2 in 7 and 1 patients respectively.

Conclusions

22 variants have been identified associated with TDH. All described novel mutations occur in domains important for protein structure and function, predicting the TDH phenotype.

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Title: Mutational screening of the TPO and DUOX2 genes in Argentinian children with congenital hypothyroidism due to thyroid dyshormonogenesis
Authors: Maricel F. Molina
Patricia Papendieck
Gabriela Sobrero
Viviana A. Balbi
Fiorella S. Belforte
Elena Bueno Martínez
Ezequiela Adrover
María C. Olcese
Ana Chiesa
Mirta B. Miras
Verónica G. González
Mauricio Gomes Pio
Rogelio González-Sarmiento
Héctor M. Targovnik
Carina M. Rivolta
Publication date: 04-05-2022
Publisher: Springer US
Keywords: Goiter
Hypothyroidism
Published in: Endocrine / Issue 1/2022
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-022-03054-3

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