Details Of Published TSH Receptor Mutation
Ile 568 Thr
c.1703T>CConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default
Clinical Features:
based on 17 hot nodules investigated by Parma et al. 1995 and 1997, Fuhrer et al. 1997, Trülzsch et al. 2001, Van Sande et al. 1995, Gozu et al. 2006, Georgopoulus et al. 2003, Nishihara et al. 2009, Eszlinger et al. 2014
and 2 activating sporadic germline mutations investigated by Tonacchera et al. 2000 and Watkins et al. 2008
and 2 activating sporadic germline mutations investigated by Tonacchera et al. 2000 and Watkins et al. 2008
Treatment:
Eszlinger et al. lobectomy
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.2
0.9
0.8-2.2
0.8
-
0.4-0.7
17
25.6+/-6.3
1,10,11
Legend:
cAMP (basal): basal in vitro cAMP production of mutant over wild-type TSHR
cAMP (TSH): maximal in vitro cAMP production of mutant over wild-type TSHR
IP (basal): basal in vitro IP production of mutant over wild-type TSHR
IP (TSH): maximal in vitro IP production of mutant over wild-type TSHR
TSH-binding: maximal TSH-binding compared to the wild-type TSHR
Cell surface expression: cell surface expression of mutant compared to WT-TSHR
LRA: linear regression analysis (LRA) of constitutive activity as a function of TSHR expression determined by 125I-bTSH binding or FACS analysis compared to the wild-type TSHR
Prevalence: Prevalence of (somatic and germline) activating mutations*
Ref: Reference for functional characterization
Child: Found in children.
Reference 1:
Parma et al.
Mol. Endocrinol. 9: 725-733
Somatic mutations causing constitutive activity of the thyrotropin receptor are the major cause of hyperfunctioning thyroid adenomas: identification of additional mutations activating both the cyclic adenosine 3',5'-monophosphate and inositol phosphate-Ca
1995
Reference 2:
Parma et al.
J. Clin. Endocrinol. Metab. 82: 2695-2701
Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas
1997
Reference 3:
Fuhrer et al.
J. Clin. Endocrinol. Metab. 82: 3885-3891
Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules
1997
Reference 4:
Trülzsch et al.
J. Mol. Med. 78: 684-691
Detection of thyroid-stimulating hormone receptor and Gsalpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis.
2001
Reference 5:
Van Sande et al.
J. Clin. Endocrinol. Metab. 80: 2577-2585
Somatic and germline mutations of the TSH receptor gene in thyroid diseases
1995
Reference 6:
Gozu et al.
Eur J Endocrinol. 155: 535-45
Similar prevalence of somatic TSH receptor and Gsalpha mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey.
2006
Reference 7:
Palos-Paz et al.
Eur J Endocrinol. 159: 623-31
Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine-deficient area in NW Spain.
2008
Reference 8:
Georgopoulos et al.
Eur J Endocrinol. 149: 287-92
Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway.
2003
Reference 9:
Nishihara et al.
Endocr J. 56:791-8
Prevalence of TSH receptor and Gsalpha mutations in 45 autonomously functioning thyroid nodules in Japan.
2009
Reference 10:
Lüblinghoff et al.
J Endocrinol Invest 33:228-233
Lack of consistent association of thyrotropin receptor mutations in vitro activity with the clinical course of patients with sporadic non-autoimmune hyperthyroidism.
2010
Reference 11:
Neumann et al.
Eur J Endocrinol 152:625-634
Interactions between the extracellular domain and the extracellular loops as well as the 6th transmembrane domain are necessary for TSH receptor activation.
2005
Reference 12:
Eszlinger, Markus, et al.
Molecular and cellular endocrinology
Somatic mutations in 33 benign and malignant hot thyroid nodules in children and adolescents
2014