دورية أكاديمية
Digenic DUOX1 and DUOX2 mutations in cases with congenital hypothyroidism
| العنوان: | Digenic DUOX1 and DUOX2 mutations in cases with congenital hypothyroidism |
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| المؤلفون: | Aycan, Zehra, Cangül, Hakan, Muzza, Marina, Bas, Veysel N., Fugazzola, Laura, Chatterjee, V. Krishna, Persani, Luca, Schoenmakers, Nadia |
| بيانات النشر: | Oxford University Press Inc |
| سنة النشر: | 2017 |
| المجموعة: | İstanbul Medipol University Institutional Repository (DSpace@Medipol) |
| مصطلحات موضوعية: | Digenic DUOX1, DUOX2, Mutations, Congenital Hypothyroidism |
| الوصف: | WOS: 000409352800001 ; PubMed ID: 28633507 ; Context: The DUOX2 enzyme generates hydrogen peroxide (H2O2), a crucial electron acceptor for the thyroid peroxidase-catalyzed iodination and coupling reactions mediating thyroid hormone biosynthesis. DUOX2 mutations result in dyshormonogenetic congenital hypothyroidism (CH) that may be phenotypically heterogeneous, leading to the hypothesis that CH severity may be influenced by environmental factors (e.g., dietary iodine) and oligogenic modifiers (e.g., variants in the homologous reduced form of NAD phosphate-oxidase DUOX1). However, loss-of-function mutations in DUOX1 have not hitherto been described, and its role in thyroid biology remains undefined. Case Description: We previously described a Proband and her brother (P1, P2) with unusually severe CH associated with a DUOX2 homozygous nonsense mutation (p.R434(star)); P1, P2: thyrotropin >100 mu U/mL [reference range (RR) 0.5 to 6.3]; and P1: free T4 (FT4) <0.09 ng/dL (RR 0.9 to 2.3). Subsequent studies have revealed a homozygous DUOX1 mutation (c.1823-1G>C) resulting in aberrant splicing and a protein truncation (p.Val607Aspfs(star)43), which segregates with CH in this kindred. Conclusion: This is a report of digenic mutations in DUOX1 and DUOX2 in association with CH, and we hypothesize that the inability of DUOX1 to compensate for DUOX2 deficiency in this kindred may underlie the severe CH phenotype. Our studies provide evidence for a digenic basis for CH and support the notion that oligogenicity as well as environmental modulators may underlie phenotypic variability in genetically ascertained CH. ; Wellcome Trust [100585/Z/12/Z, 095564/Z/11/Z]; National Institutes for Health Research Cambridge Biomedical Research Centre; Italian Ministry of Health [RF-2010-2309484]; TUBITAK: The Scientific and Technological Research Council of Turkey [214S637] ; This work was supported by Wellcome Trust Grants 100585/Z/12/Z (to N.S.) and 095564/Z/11/Z (to V.K.C.); National Institutes for Health Research Cambridge ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0021-972X 1945-7197 |
| العلاقة: | Journal of Clinical Endocrinology & Metabolism; info:eu-repo/grantAgreement/TUBITAK/SOBAG/214S637; Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı; Aycan, Z., Cangül, H., Muzza, M., Bas, V. N., Fugazzola, L., Chatterjee, V. K. … Schoenmakers, N. (2017). Digenic DUOX1 and DUOX2 mutations in cases with congenital hypothyroidism. Journal of Clinical Endocrinology & Metabolism, 102(9), 3085-3090. https://dx.doi.org/10.1210/jc.2017-00529Test; https://dx.doi.org/10.1210/jc.2017-00529Test; https://hdl.handle.net/20.500.12511/3026Test; 102; 3085; 3090; Q1 |
| DOI: | 10.1210/jc.2017-00529 |
| الإتاحة: | https://doi.org/20.500.12511/3026Test https://doi.org/10.1210/jc.2017-00529Test https://hdl.handle.net/20.500.12511/3026Test |
| حقوق: | info:eu-repo/semantics/openAccess ; Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.A840AB1C |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 0021972X 19457197 |
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| DOI: | 10.1210/jc.2017-00529 |