caa a22 4500 475790618 CHVBK 20180406123709.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1007/s004230000145 doi (NATIONALLICENCE)springer-10.1007/s004230000145 Constitutively activating TSH-receptor mutations as a molecular cause of non-autoimmune hyperthyroidism in childhood [Elektronische Daten] [Heike Biebermann, Torsten Schöneberg, Heiko Krude, Thomas Gudermann, Annette Grüters] Abstract.: Background: The glycoprotein hormone TSH (thyroid-stimulating hormone) and its receptor, the TSH-receptor (TSHR), play a crucial role in thyroid growth and function. Constitutively activating germline mutations within the TSHR gene were identified in patients with sporadic or familial non-autoimmune hyperthyroidism. Inheritance of these mutations is autosomal dominant. Patients and methods: We investigated two patients with neonatal onset of non-autoimmune hyperthyroidism and two families in whom the child and one parent are affected. Results: Hyperthyroidism was difficult to treat in all of these patients and was complicated by premature craniosynostosis. Sequencing of all exons of the TSHR gene in one family with hyperthyroidism revealed a mutation in exon 10 (T632I), which was first identified in toxic adenomas and found to constitutively activate the TSHR. In the other family, we identified a new mutation in the first membrane spanning segment (G431S). In both patients with sporadic hyperthyroidism, a heterozygous mutation in exon 9 (S281N) was detected. The functional characterization of S281N and G431S demonstrated that both mutants were constitutively active. Therefore, these mutations are the molecular cause of non-autoimmune hyperthyroidism in the patients. Conclusions: For patients suffering from non-autoimmune hyperthyroidism, screening for mutations and their functional characterization is recommended. In case of an ineffective hyperthyroidism treatment, thyroidectomy should be performed to prevent lengthy anti-thyroid drug treatment and complications like premature craniosynostosis. Springer-Verlag, 2000 Non-autoimmune hyperthyroidism TSHR Mutation Constitutive activity nationallicence Biebermann Heike Klinik und Poliklinik für Kinderheilkunde, Virchow-Klinikum, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany, Germany aut Schöneberg Torsten Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Thielallee 69-73, 14195 Berlin, Germany, Germany aut Krude Heiko Klinik und Poliklinik für Kinderheilkunde, Virchow-Klinikum, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany, Germany aut Gudermann Thomas Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Thielallee 69-73, 14195 Berlin, Germany, Germany aut Grüters Annette Klinik und Poliklinik für Kinderheilkunde, Virchow-Klinikum, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany, Germany aut Langenbeck's Archives of Surgery Springer-Verlag 385/6(2000-10-01), 390-392 1435-2443 385:6<390 2000 385 423 https://doi.org/10.1007/s004230000145 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004230000145 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Biebermann Heike Klinik und Poliklinik für Kinderheilkunde, Virchow-Klinikum, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany, Germany aut NATIONALLICENCE 700 1- Schöneberg Torsten Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Thielallee 69-73, 14195 Berlin, Germany, Germany aut NATIONALLICENCE 700 1- Krude Heiko Klinik und Poliklinik für Kinderheilkunde, Virchow-Klinikum, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany, Germany aut NATIONALLICENCE 700 1- Gudermann Thomas Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Thielallee 69-73, 14195 Berlin, Germany, Germany aut NATIONALLICENCE 700 1- Grüters Annette Klinik und Poliklinik für Kinderheilkunde, Virchow-Klinikum, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany, Germany aut NATIONALLICENCE 773 0- Langenbeck's Archives of Surgery Springer-Verlag 385/6(2000-10-01), 390-392 1435-2443 385:6<390 2000 385 423 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer