دورية أكاديمية
DUOX2 Mutations Are Associated With Congenital Hypothyroidism With Ectopic Thyroid Gland.
| العنوان: | DUOX2 Mutations Are Associated With Congenital Hypothyroidism With Ectopic Thyroid Gland. |
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| المؤلفون: | Kizys MML; Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil., Louzada RA; UMR 8200 CNRS, Villejuif, 94800, France.; Institut Gustave Roussy, Villejuif, 94800, France.; Université Paris-Saclay, Orsay, 91405, France.; Laboratory of Endocrine Physiology Doris Rosenthal, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil., Mitne-Neto M; Fleury Group, São Paulo 04344-070, Brazil.; Human Genome and Stem Cell Research Center, Biosciences Institute, Universidade de São Paulo, São Paulo 05508-900, Brazil., Jara JR; Department of Pediatrics, Universidade Federal do Paraná, Curitiba 80060-240, Brazil., Furuzawa GK; Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil., de Carvalho DP; Laboratory of Endocrine Physiology Doris Rosenthal, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil., Dias-da-Silva MR; Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil., Nesi-França S; Department of Pediatrics, Universidade Federal do Paraná, Curitiba 80060-240, Brazil., Dupuy C; UMR 8200 CNRS, Villejuif, 94800, France.; Institut Gustave Roussy, Villejuif, 94800, France.; Université Paris-Saclay, Orsay, 91405, France., Maciel RMB; Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil.; Fleury Group, São Paulo 04344-070, Brazil. |
| المصدر: | The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2017 Nov 01; Vol. 102 (11), pp. 4060-4071. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Springfield, Ill. : Charles C. Thomas |
| مواضيع طبية MeSH: | Mutation*, Congenital Hypothyroidism/*genetics , Dual Oxidases/*genetics , Thyroid Dysgenesis/*genetics, Cohort Studies ; Congenital Hypothyroidism/complications ; DNA Mutational Analysis ; Dual Oxidases/chemistry ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; HEK293 Cells ; Humans ; Infant, Newborn ; Male ; Protein Domains/genetics ; Thyroid Dysgenesis/complications ; Thyroid Gland/embryology |
| مستخلص: | Context: Thyroid dysgenesis (TD) is the leading cause of congenital hypothyroidism (CH). The etiology of TD remains unknown in ∼90% of cases, the most common form being thyroid ectopia (TE) (48% to 61%). Objective: To search for candidate genes in hypothyroid children with TE. Design, Setting, and Participants: We followed a cohort of 268 children with TD and performed whole-exome sequencing (WES) in three children with CH with TE (CHTE) and compared them with 18 thyroid-healthy controls. We then screened an additional 41 children with CHTE by Sanger sequencing and correlated the WES and Sanger molecular findings with in vitro functional analysis. Main Outcome Measures: Genotyping, mutation prediction analysis, and in vitro functional analysis. Results: We identified seven variants in the DUOX2 gene, namely G201E, L264CfsX57, P609S, M650T, E810X, M822V, and E1017G, and eight known variations. All children carrying DUOX2 variations had high thyroid-stimulating hormone levels at neonatal diagnosis. All mutations were localized in the N-terminal segment, and three of them led to effects on cell surface targeting and reactive oxygen species generation. The DUOX2 mutants also altered the interaction with the maturation factor DUOXA2 and the formation of a stable DUOX2/DUOXA2 complex at the cell surface, thereby impairing functional enzymatic activity. We observed no mutations in the classic genes related to TD or in the DUOX1 gene. Conclusion: Our findings suggest that, in addition to thyroid hormonogenesis, the DUOX2 N-terminal domain may play a role in thyroid development. (Copyright © 2017 Endocrine Society) |
| المشرفين على المادة: | EC 1.11.1.- (Dual Oxidases) EC 1.6.3.1 (DUOX2 protein, human) |
| تواريخ الأحداث: | Date Created: 20170702 Date Completed: 20171204 Latest Revision: 20180518 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1210/jc.2017-00832 |
| PMID: | 28666341 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-7197 |
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| DOI: | 10.1210/jc.2017-00832 |