A Novel Thyrotropin Receptor Germline Mutation (Asp617Tyr) Causing Hereditary Hyperthyroidism
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- NISHIHARA Eijun
- Kuma Hospital
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- NAGAYAMA Yuji
- Department of Medical Gene Technology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences
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- AMINO Nobuyuki
- Kuma Hospital
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- HISHINUMA Akira
- Department of Clinical Laboratory Medicine, Dokkyo University School of Medicine
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- TAKANO Toru
- Department of Laboratory Medicine, Osaka University Graduate School of Medicine
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- YOSHIDA Hiroshi
- Kuma Hospital
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- KUBOTA Sumihisa
- Kuma Hospital
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- FUKATA Shuji
- Kuma Hospital
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- KUMA Kanji
- Kuma Hospital
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- MIYAUCHI Akira
- Kuma Hospital
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Abstract
Constitutively activating germline mutations of the thyrotropin receptor (TSHR) gene have been identified as a molecular cause of hereditary nonautoimmune hyperthyroidism. We describe here a Japanese kindred with two affected individuals who showed overt hyperthyroidism and mild goiter in the absence of TSHR antibodies. A novel heterozygous germline point mutation, identified in both individuals, resulted in an amino acid substitution of aspartic acid for tyrosine at codon 617 (Asp617Tyr) in the third intracellular loop of the TSHR. Screening of 7 additional family members led to the identification of the same mutation in 4 relatives: 1 had undergone thyroidectomy due to hyperthyroidism but 3 were asymptomatic with subclinical hyperthyroidism. In vitro functional studies of the Asp617Tyr TSHR demonstrated a constitutive activation of the cyclic adenosine monophosphate pathway, but not of the inositol phosphate cascade, with data similar to those of Asp619Gly, the first constitutively activating mutant TSHR identified. Treatment with inorganic iodine for 7 months successfully relieved all symptoms of hyperthyroidism in both patients.<br>
Journal
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- Endocrine Journal
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Endocrine Journal 54 (6), 927-934, 2007
The Japan Endocrine Society
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Details 詳細情報について
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- CRID
- 1390001206299060480
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- NII Article ID
- 10021263788
- 130004443343
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- NII Book ID
- AA10901436
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- ISSN
- 13484540
- 09188959
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed