DUOX2/DUOXA2 Mutations Frequently Cause Congenital Hypothyroidism that Evades Detection on Newborn Screening in the United Kingdom
| Autor: | Nadia Schoenmakers, Erik Schoenmakers, Catherine Peters, Shirley Langham, Neil J. Sebire, Eva Goncalves Serra, Marina Muzza, Adeline K Nicholas, Greta Lyons, Laura Fugazzola |
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| Přispěvatelé: | Schoenmakers, Erik [0000-0003-0674-8282], Schoenmakers, Nadia [0000-0002-0847-2884], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty dyshormonogenesis endocrine system diseases Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism 03 medical and health sciences 0302 clinical medicine Endocrinology Neonatal Screening medicine Humans DUOX2 gland in situ Newborn screening business.industry gland Infant Newborn DUOXA2 Membrane Proteins congenital hypothyroidism medicine.disease Infant newborn Dual Oxidases United Kingdom 3. Good health Congenital hypothyroidism Cross-Sectional Studies 030220 oncology & carcinogenesis Mutation (genetic algorithm) Mutation Etiology Female business Thyroid Dysfunction: Hypothyroidism Thyrotoxicosis and Thyroid Function Tests |
| Zdroj: | Thyroid |
| ISSN: | 1557-9077 1050-7256 |
| Popis: | Background: The etiology, course, and most appropriate management of borderline congenital hypothyroidism (CH) are poorly defined, such that the optimal threshold for diagnosis with bloodspot screening thyrotropin (bsTSH) measurement remains controversial. Dual oxidase 2 (DUOX2) mutations may initially cause borderline elevation of bsTSH, which later evolves into significant hypothyroidism on venous blood measurement. It was hypothesized that mutations in both DUOX2 and its accessory protein DUOXA2 may occur frequently, even in patients with borderline bsTSH elevation, such that higher diagnostic thresholds in bsTSH screening may fail to detect such cases, with consequent risk of undiagnosed neonatal hypothyroidism of sufficient magnitude to require thyroxine therapy. This study aimed to investigate the frequency and characteristics of DUOX2 and DUOXA2 mutations in a borderline CH cohort. Methods: A cross-sectional study of patients with borderline CH was undertaken at Great Ormond Street Hospital, a tertiary British pediatric center. DUOX2 was sequenced in 52 patients with a bsTSH of 6-19.9 mIU/L, venous TSH of >25 mIU/L, and eutopic thyroid gland in situ. DUOXA2 was sequenced in DUOX2 mutation-negative cases, and novel DUOXA2 mutations were functionally characterized. Results: A total of 26 (50%) patients harbored likely pathogenic mutations in DUOX2 (n = 20; 38%) or DUOXA2 (n = 6; 12%), including novel gene variants (DUOX2, n = 3; DUOXA2, n = 7). Two recurrent DUOX2 mutations (p.Q570L, p.F966Sfs*29) occurred frequently in population databases (MAF ≥0.01). Despite bsTSH being |
| Databáze: | OpenAIRE |
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