2010 Fiscal Year Final Research Report
Molecular Mechanisms and Pathophysiology of Congenital Hypothyroidism
| Project/Area Number |
20591232
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Keio University |
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Principal Investigator |
HASEGAWA Tomonobu Keio University, 医学部, 准教授 (20189533)
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| Research Collaborator |
NARUMI Satoshi 慶應義塾大学, 医学部, 助教 (21791006)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 小児内分泌学 / 先天性甲状腺機能低下症 |
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| Research Abstract |
(1)The prevalence on monogenic disease in Japanese congenital hypothyroidism(CH), 1.biallelic TSHR mutations ; 4.3% in moderate to severe CH, 2.PAX8 mutations ; 2.0% in CH, 3.bialelic DUOX2 mutations ; 7.8% in CH, 4.TG mutations ; 4.9% in CH, 5.TPO mutations ; 2.0% in CH, 6.Other mutations ; rare. (2)Polygenic disease; one CH patient having digenic mutations of TSHR and DUOX2. (3)In vitro experiments confirmed loss of functions of 1. four mutations of TSHR, namely G132R, A204V, D403N, R450H, having reduced binding activities and cAMP responses, and 2. K80_A84dup PAX8 localizing in nucleus, but having severely impaired DNA binding and transactivation.
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