{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:29:34Z","timestamp":1783484974128,"version":"3.55.0"},"reference-count":30,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,12,1]]},"abstract":"<jats:p>Constitutively activating germline mutations in the TSH receptor (TSHR) gene have been identified as a cause of autosomal dominant nonautoimmune hyperthyroidism and sporadic congenital hyperthyroidism. We report a 10-yr-old boy and his 31-yr-old mother, both presenting with a history of recurring toxic thyroid hyperplasia and no evidence for autoimmune thyroid disease. In the boy, onset of hyperthyroidism and goiter was neonatal. In the mother, onset of thyroid disease dates back to early childhood. There was no history of thyroid disease in the rest of the family. Screening for germline mutations in exon 10 of the TSHR was performed by direct sequencing of genomic DNA extracted from peripheral blood leukocytes of both patients. In the boy and his mother, an identical heterozygous TSHR mutation was identified, exchanging leucine for phenylalanine at residue 629 of the TSHR (TTG\u2192TTT). Transient expression of the mutated TSHR construct in COS-7 cells confirmed the constitutive activity of the new TSHR germline mutation. This is the second family displaying congenital manifestation of hyperthyroidism in familial nonautoimmune hyperthyroidism.<\/jats:p>","DOI":"10.1210\/jcem.82.12.4405","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:01:01Z","timestamp":1389200461000},"page":"4234-4238","source":"Crossref","is-referenced-by-count":35,"title":["Identification of a New Thyrotropin Receptor Germline Mutation (Leu629Phe) in a Family with Neonatal Onset of Autosomal Dominant Nonautoimmune Hyperthyroidism"],"prefix":"10.1210","volume":"82","author":[{"given":"Dagmar","family":"Fu\u0308hrer","sequence":"first","affiliation":[{"name":"Third Medical Department and Pediatric Clinic (H.W.), University of Leipzig, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Wonerow","sequence":"additional","affiliation":[{"name":"Third Medical Department and Pediatric Clinic (H.W.), University of Leipzig, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Willgerodt","sequence":"additional","affiliation":[{"name":"Third Medical Department and Pediatric Clinic (H.W.), University of Leipzig, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Paschke","sequence":"additional","affiliation":[{"name":"Third Medical Department and Pediatric Clinic (H.W.), University of Leipzig, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0357-4192","authenticated-orcid":false,"given":"Dagmar","family":"F\u00fchrer-Sakel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[1997,12,1]]},"reference":[{"key":"2021081912013532300_R1","author":"McLachlan","year":"1996"},{"key":"2021081912013532300_R2","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1530\/acta.0.1000512","article-title":"Familial hyperthyroidism without evidence of autoimmunity.","volume":"100","author":"Thomas","year":"1982","journal-title":"Acta Endocrinol (Copenh)"},{"key":"2021081912013532300_R3","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/ng0794-396","article-title":"Germline mutations in the thyrotropin receptor gene cause nonautoimmune autosomal dominant hyperthyroidism.","volume":"7","author":"Duprez","year":"1994","journal-title":"Nat Genet"},{"key":"2021081912013532300_R4","first-page":"92","article-title":"Hereditary hyperthyroidism with diffuse non autoimmune hyperactivity due to autonomy of function and growth [Abstract].","volume":"48","author":"Horton","year":"1987","journal-title":"Ann Endocrinol (Paris)"},{"key":"2021081912013532300_R5","first-page":"547","article-title":"Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic thyroid hyperplasia.","volume":"81","author":"Tonacchera","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2021081912013532300_R6"},{"key":"2021081912013532300_R7","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1055\/s-0029-1211719","article-title":"Mutations of the TSH receptor as a cause of congenital hyperthyroidism.","volume":"104","author":"Schwab","year":"1996","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"2021081912013532300_R8","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1152\/physrev.1992.72.3.667","article-title":"Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors.","volume":"72","author":"Dumont","year":"1992","journal-title":"Physiol Rev"},{"key":"2021081912013532300_R9","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/j.1460-2075.1992.tb05084.x","article-title":"Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism.","volume":"11","author":"Ledent","year":"1992","journal-title":"EMBO J"},{"key":"2021081912013532300_R10","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1210\/jcem-59-1-175","article-title":"Behaviour of thyroid tissue from patients with Graves\u2019 disease in nude mice.","volume":"59","author":"Leclere","year":"1984","journal-title":"J Clin Endocrinol Metab"},{"key":"2021081912013532300_R11","first-page":"116","article-title":"Phenotype of familial non autoimmune diffuse thyrotoxicosis[ Abstract].","volume":"231","author":"Leclere","year":"1995","journal-title":"Thyroid"},{"key":"2021081912013532300_R12","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1056\/NEJM199501193320304","article-title":"Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene.","volume":"332","author":"Kopp","year":"1995","journal-title":"N Engl J Med"},{"key":"2021081912013532300_R13","first-page":"2023","article-title":"A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism.","volume":"81","author":"De Roux","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2021081912013532300_R14"},{"key":"2021081912013532300_R15","first-page":"71","article-title":"A novel TSH receptor mutation in an infant with thyrotoxicosis[ Abstract].","volume":"19","author":"Esapa","year":"1996","journal-title":"J Endocrinol Invest"},{"key":"2021081912013532300_R16","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0303-7207(95)03753-5","article-title":"Microsatellites and PCR primers for genetic studies and genomic sequencing of the human TSH receptor gene.","volume":"117","author":"De Roux","year":"1996","journal-title":"Mol Cell Endocrinol"},{"key":"2021081912013532300_R17","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/nar\/21.1.173","article-title":"Large-scale production of DNA sequencing templates by microtitre format PCR.","volume":"21","author":"Rosenthal","year":"1993","journal-title":"Nucleic Acids Res"},{"key":"2021081912013532300_R18","author":"Ausubel","year":"1996"},{"key":"2021081912013532300_R19","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/S0026-895X(25)08761-9","article-title":"Interpretation of binding curves with high receptor concentrations: practical aid for computer analysis.","volume":"47","year":"1995","journal-title":"Mol Pharmacol"},{"key":"2021081912013532300_R20","first-page":"2577","article-title":"Genetic basis of endocrine disease. Somatic and germline mutations of the TSH receptor gene in thyroid diseases.","volume":"80","author":"Van Sande","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2021081912013532300_R21","first-page":"1785","article-title":"Identification and functional characterization of two new somatic mutations causing constitutive activation of the TSH receptor in hyperfunctioning autonomous adenomas of the thyroid.","volume":"79","author":"Paschke","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"2021081912013532300_R22","author":"Parma","year":"1997"},{"key":"2021081912013532300_R23","first-page":"725","article-title":"Somatic mutations causing constitutive activity of the TSH receptor are the major cause of hyperfunctional thyroid adenomas: identification of additional mutations activating both the cAMP and inositolphosphate-Ca2+-cascades.","volume":"9","author":"Parma","year":"1995","journal-title":"Mol Endocrinol"},{"key":"2021081912013532300_R24"},{"key":"2021081912013532300_R25","author":"McKusick","year":"1992"},{"key":"2021081912013532300_R26","first-page":"1009","article-title":"Activation of the thyrotropin (TSH) receptor by human chorionic gonadotropin and luteinizing hormone in chinese hamster ovary cells expressing functional human TSH receptors.","volume":"77","author":"Yoshimura","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"key":"2021081912013532300_R27","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1089\/thy.1995.5.425","article-title":"Thyrotropic action of human chorionic gonadotropin.","volume":"5","author":"Yoshimura","year":"1995","journal-title":"Thyroid"},{"key":"2021081912013532300_R28","first-page":"1333","article-title":"Therole of chorionic gonadotrophin intransient hyperthyroidism of hyperemesis gravidarum.","volume":"75","author":"Goodwin","year":"1992","journal-title":"J Clin Endocrinol Metab"},{"key":"2021081912013532300_R29","first-page":"913","article-title":"Hyperthyroidism induced bytrophoblastic thyrotropin.","volume":"47","year":"1972","journal-title":"Mayo Clin Proc"},{"key":"2021081912013532300_R30","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1002\/cncr.2820690535","article-title":"Hyperthyroidism in men with germ cell tumors and high levels of beta-chorionic gonadotrophin.","volume":"69","author":"Giralt","year":"1992","journal-title":"Cancer"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/82\/12\/4234\/39806266\/jcem_82_12_4234.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/82\/12\/4234\/39806266\/jcem_82_12_4234.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T11:57:07Z","timestamp":1746100627000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/82\/12\/4234\/2866096"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,12,1]]},"references-count":30,"journal-issue":{"issue":"12","published-online":{"date-parts":[[1997,12,1]]},"published-print":{"date-parts":[[1997,12,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jcem.82.12.4405","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1997,12,1]]},"published":{"date-parts":[[1997,12,1]]}}}