Genetics and phenomics of inherited and sporadic non-autoimmune hyperthyroidism

被引:45
作者
Gozu, Hulya Iliksu [1 ]
Lublinghoff, Julia [2 ]
Bircan, Rifat [3 ]
Paschke, Ralf [2 ]
机构
[1] Vakif Gureba Educ & Res Hosp, Sect Endocrinol & Metab, TR-34093 Istanbul, Turkey
[2] Univ Leipzig, Dept Internal Med 3, Leipzig, Germany
[3] Namik Kemal Univ, Fac Arts & Sci, Div Biol, Dept Mol Biol, TR-59030 Tekirdag, Turkey
关键词
Germline TSH receptor mutations; THYROTROPIN RECEPTOR GENE; ACTIVATING GERMLINE MUTATION; STIMULATING HORMONE-RECEPTOR; TERM-FOLLOW-UP; TSH RECEPTOR; CONGENITAL HYPERTHYROIDISM; NONAUTOIMMUNE HYPERTHYROIDISM; FAMILIAL HYPERTHYROIDISM; EXPRESSION; THYROTOXICOSIS;
D O I
10.1016/j.mce.2010.02.001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
TSH receptor (TSHR) germline mutations occur as activating mutations in familial non-autoimmune hyperthyroidism (FNAH) or sporadic non-autoimmune hyperthyroidism (SNAH). Up to date 17 constitutively activating TSHR mutations have been reported in 24 families with FNAH. The diagnosis of FNAH should be considered in cases with a positive family history, early onset of hyperthyroidism, goiter, absence of clinical stigmata of autoimmunity and recurrent hyperthyroidism. Moreover, 14 subjects with sporadic non-autoimmune hyperthyroidism and 10 different TSH receptor germline mutations have been reported. The main characteristic of SNAH is a negative family history. Additional consequences of prolonged neonatal hyperthyroidism (mental retardation, speech disturbances and craniosynostosis) have often been reported in SNAH. No genotype-phenotype relationship has been reported in patients with germline TSHR mutations. There is no association of in vitro activities determined by linear regression analysis (LRA) and several clinical indicators of hyperthyroidism activity for SNAH. However, the comparison of the LRA values of sporadic TSHR mutations with LRA values of familial TSHR mutations does show a significantly higher median LRA value for sporadic as compared to familial autosomal dominant hyperthyroidism. This finding is in line with the clinical impression of a more active clinical course in patients with SNAH. However, additional genetic, constitutional or environmental factors are most likely responsible for the phenotypic variations of the disease and the lack of correlation between in vitro activities of the TSHR mutations and the severity of hyperthyroidism. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:125 / 134
页数:10
相关论文
共 65 条
[1]   A family with a novel TSH receptor activating germline mutation (p.Ala485Val) [J].
Akcurin, Sema ;
Turkkahraman, Doga ;
Tysoe, Carolyn ;
Ellard, Sian ;
De Leener, Anne ;
Vassart, Gilbert ;
Costagliola, Sabine .
EUROPEAN JOURNAL OF PEDIATRICS, 2008, 167 (11) :1231-1237
[2]   A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism [J].
Alberti, L ;
Proverbio, MC ;
Costagliola, S ;
Weber, G ;
Beck-Peccoz, P ;
Chiumello, G ;
Persani, L .
EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2001, 145 (03) :249-254
[3]  
ALLGEIER A, 1994, J BIOL CHEM, V269, P13733
[4]   Similarities and differences in the phenotype of members of an Italian family with hereditary non-autoimmune hyperthyroidism associated with an activating TSH receptor germline mutation [J].
Arturi, F ;
Chiefari, E ;
Tumino, S ;
Russo, D ;
Squatrito, S ;
Chazenbalk, G ;
Persani, L ;
Rapoport, B ;
Filetti, S .
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 2002, 25 (08) :696-701
[5]   The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism [J].
Biebermann, H ;
Schöneberg, T ;
Hess, C ;
Germak, J ;
Gudermann, T ;
Grüters, A .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (09) :4429-4433
[6]   Multiple relapses of hyperthyroidism after thyroid surgeries in a patient with long term follow-up of sporadic non-autoimmune hyperthyroidism [J].
Bircan, R. ;
Miehle, K. ;
Mladenova, G. ;
Ivanova, R. ;
Ivanova, R. ;
Sarafova, A. ;
Borissova, A. -M. ;
Lueblinghoff, J. ;
Paschke, R. .
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 2008, 116 (06) :341-346
[7]   Long-term carbimazole treatment of neonatal nonautoimmune hyperthyroidism due to a new activating TSH receptor gene mutation (Ala428Val) [J].
Börgel, K ;
Pohlenz, J ;
Koch, HG ;
Bramswig, JH .
HORMONE RESEARCH, 2005, 64 (04) :203-208
[8]  
Chester J, 2008, J PEDIATR ENDOCR MET, V21, P479
[9]   Novel thyrotropin receptor germline mutation (IIe568Val) in a saxonian family with hereditary nonautoimmune hyperthyroidism [J].
Claus, M ;
Maier, J ;
Paschke, R ;
Kujat, C ;
Stumvoll, M ;
Führer, D .
THYROID, 2005, 15 (09) :1089-1094
[10]   A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism [J].
DeRoux, N ;
Polak, M ;
Couet, J ;
Leger, J ;
Czernichow, P ;
Milgrom, E ;
Misrahi, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (06) :2023-2026