A Novel Thyrotropin Receptor Germline Mutation (Asp617Tyr) Causing Hereditary Hyperthyroidism

Endocrine Journal

Hiroshi YOSHIDA¹  Akira MIYAUCHI¹  Akira HISHINUMA²  Eijun NISHIHARA¹  Sumihisa KUBOTA¹  Nobuyuki AMINO¹  Kanji KUMA¹  Shuji FUKATA¹  Toru TAKANO⁴  Yuji NAGAYAMA³ 

[1] Kuma Hospital;Department of Clinical Laboratory Medicine, Dokkyo University School of Medicine;Department of Medical Gene Technology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences;Department of Laboratory Medicine, Osaka University Graduate School of Medicine

关键词: Thyrotropin receptor;    Germline mutation;    Nonautoimmune hyperthyroidism;    Adenylyl cyclase activation;    Third intracellular loop;   

DOI  :  10.1507/endocrj.K07-088

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(36)Cited-By(10)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.

【 授权许可】

Unknown