Details Of Published TSH Receptor Mutation
Thr 632 Ile
c.1895C>TConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default
Clinical Features:
based on 58 hot nodules investigated by Paschke et al. 1994, Parma et al. 1997, Duprez et al. 1997, Russo et al. 1996, Holzapfel et al. 1997, Porcellini et al. 1994, Tonacchera et al. 1998, Fuhrer et al. 1997, Tassi et al. 1999, Derwahl et al. 1996, Tonacchera et al. 2000, Georgopoulos et al. 2003, Gozu et al. 2005 and 2006, Trulzsch et al. 2001, Palos-Paz et al. 2008, Stephenson et al. 2020, Sancak et al. 2011, Nishihara et al. 2009, Schwab et al. 2009, Tonacchera et al. 1999, Eszlinger et al. 2014.
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.7-5.0
0.8-1.0
1.0-1.3
0.7-1.0
n.d.
58
1,3,5
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:
Fuhrer et al.
J. Clin. Endocrinol. Metab. 82: 4234-4238
Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism
1997
Reference 2:
Holzapfel et al.
J. Clin. Endocrinol. Metab. 82: 3879-3884
Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene
1997
Reference 3:
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 4:
Paschke et al.
J. Clin. Endocrinol. Metab. 79: 1785-1789
Identification and functional characterization of two new somatic mutations causing constitutive activation of the thyrotropin receptor in hyperfunctioning autonomous adenomas of the thyroid
1994
Reference 5:
Porcellini et al.
J. Clin. Endocrinol. Metab. 79: 657-661
Novel mutations of thyrotropin receptor gene in thyroid hyperfunctioning adenomas. Rapid identification by fine needle aspiration biopsy
1994
Reference 6:
Duprez et al.
J. Clin. Endocrinol. Metab. 82: 306-308
Two autonomous nodules of a patient with multinodular goiter harbor different activating mutations of the thyrotropin receptor gene
1997
Reference 7:
Russo et al.
J. Clin. Endocrinol. Metab. 81: 1548-1551
Thyrotropin receptor gene alterations in thyroid hyperfunctioning adenomas
1996
Reference 8:
Tonacchera et al.
J. Clin. Endocrinol. Metab. 83: 492-498
Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma
1998
Reference 9:
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 10:
Tassi et al.
Thyroid 9: 353-357
Screening of thyrotropin receptor mutations by fine-needle aspiration biopsy in autonomous functioning thyroid nodules in multinodular goiters
1999
Reference 11:
Kosugi et al.
FEBS Lett 356: 291-294
Constitutive activation of cyclic AMP but not phosphatidylinositol signaling caused by four mutations in the 6th transmembrane helix of the human thyrotropin receptor.
1994
Reference 12:
Tonacchera et al.
J Clin Endocrinol Metab. 85: 2270-4
Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter.
2000
Reference 13:
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 14:
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 15:
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 16:
Derwahl et al.
J Clin Endocrinol Metab.81: 1898-904
Constitutive activation of the Gs alpha protein-adenylate cyclase pathway may not be sufficient to generate toxic thyroid adenomas.
1996
Reference 17:
Gozu et al.
Endocr J. 52: 577-85
Mutations in the thyrotropin receptor signal transduction pathway in the hyperfunctioning thyroid nodules from multinodular goiters: a study in the Turkish population.
2005
Reference 18:
Sancak et al.
Horm Metab Res. 43:562-8
High Prevalence of TSHR/Gsalpha Mutation-negative Clonal Hot Thyroid Nodules (HNs) in a Turkish Cohort
2011
Reference 19:
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 20:
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 21:
Schwab, Karl Otfried, et al.
The Journal of Pediatrics
Autonomous thyroid adenoma: only an adulthood disease?
2009
Reference 22:
Stephenson et al.
Thyroid
Sensitive Sequencing Analysis Suggests Thyrotropin
Receptor and Guanine Nucleotide-Binding Protein G Subunit
Alpha as Sole Driver Mutations in Hot Thyroid Nodules
2020